rs60314569

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000424.4(KRT5):c.556-15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 1,613,858 control chromosomes in the GnomAD database, including 15,698 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2135 hom., cov: 32)

Exomes 𝑓: 0.13 ( 13563 hom. )

Consequence

KRT5
NM_000424.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.384

Publications

5 publications found

Variant links:

Genes affected

KRT5 (HGNC:6442): (keratin 5) The protein encoded by this gene is a member of the keratin gene family. The type II cytokeratins consist of basic or neutral proteins which are arranged in pairs of heterotypic keratin chains coexpressed during differentiation of simple and stratified epithelial tissues. This type II cytokeratin is specifically expressed in the basal layer of the epidermis with family member KRT14. Mutations in these genes have been associated with a complex of diseases termed epidermolysis bullosa simplex. The type II cytokeratins are clustered in a region of chromosome 12q12-q13. [provided by RefSeq, Jul 2008]

KRT5 Gene-Disease associations (from GenCC):

Dowling-Degos disease
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
epidermolysis bullosa simplex 1A, generalized severe
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, Ambry Genetics
epidermolysis bullosa simplex 2F, with mottled pigmentation
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, PanelApp Australia, G2P
Dowling-Degos disease 1
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
epidermolysis bullosa simplex 1B, generalized intermediate
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp
epidermolysis bullosa simplex 1C, localized
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp
epidermolysis bullosa simplex 2B, generalized intermediate
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
epidermolysis bullosa simplex 1D, generalized, intermediate or severe, autosomal recessive
Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia
epidermolysis bullosa simplex 2d, generalized, intermediate or severe, autosomal recessive
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
epidermolysis bullosa simplex 2E, with migratory circinate erythema
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

KRT5 links:

ENSG00000303401 (HGNC:):

ENSG00000303401 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 12-52519175-G-A is Benign according to our data. Variant chr12-52519175-G-A is described in ClinVar as Benign. ClinVar VariationId is 256044.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT5	NM_000424.4 link	c.556-15C>T		intron_variant	Intron 1 of 8	ENST00000252242.9	NP_000415.2	P13647

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT5	ENST00000252242.9 link	c.556-15C>T		intron_variant	Intron 1 of 8	1	NM_000424.4	ENSP00000252242.4		P13647

Frequencies

GnomAD3 genomes

AF:

0.161

AC:

24453

AN:

152048

Hom.:

2128

Cov.:

show subpopulations

Gnomad AFR

AF:

0.216

Gnomad AMI

AF:

0.270

Gnomad AMR

AF:

0.181

Gnomad ASJ

AF:

0.198

Gnomad EAS

AF:

0.0336

Gnomad SAS

AF:

0.103

Gnomad FIN

AF:

0.126

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.138

Gnomad OTH

AF:

0.188

GnomAD2 exomes

AF:

0.135

AC:

33891

AN:

251080

AF XY:

0.133

show subpopulations

Gnomad AFR exome

AF:

0.220

Gnomad AMR exome

AF:

0.152

Gnomad ASJ exome

AF:

0.204

Gnomad EAS exome

AF:

0.0303

Gnomad FIN exome

AF:

0.129

Gnomad NFE exome

AF:

0.137

Gnomad OTH exome

AF:

0.146

GnomAD4 exome

AF:

0.132

AC:

193020

AN:

1461692

Hom.:

13563

Cov.:

AF XY:

0.131

AC XY:

95309

AN XY:

727158

show subpopulations

African (AFR)

AF:

0.220

AC:

7351

AN:

33470

American (AMR)

AF:

0.156

AC:

6954

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.199

AC:

5194

AN:

26136

East Asian (EAS)

AF:

0.0247

AC:

979

AN:

39700

South Asian (SAS)

AF:

0.103

AC:

8873

AN:

86254

European-Finnish (FIN)

AF:

0.132

AC:

7067

AN:

53412

Middle Eastern (MID)

AF:

0.191

AC:

1087

AN:

5702

European-Non Finnish (NFE)

AF:

0.132

AC:

147084

AN:

1111948

Other (OTH)

AF:

0.140

AC:

8431

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

9622

19243

28865

38486

48108

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5276

10552

15828

21104

26380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.161

AC:

24491

AN:

152166

Hom.:

2135

Cov.:

AF XY:

0.161

AC XY:

11970

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.216

AC:

8978

AN:

41508

American (AMR)

AF:

0.181

AC:

2767

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.198

AC:

686

AN:

3470

East Asian (EAS)

AF:

0.0333

AC:

172

AN:

5170

South Asian (SAS)

AF:

0.103

AC:

496

AN:

4818

European-Finnish (FIN)

AF:

0.126

AC:

1331

AN:

10598

Middle Eastern (MID)

AF:

0.211

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.138

AC:

9362

AN:

67984

Other (OTH)

AF:

0.185

AC:

391

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1029

2058

3087

4116

5145

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

256

512

768

1024

1280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.101

Hom.:

204

Bravo

AF:

0.166

Asia WGS

AF:

0.0910

AC:

318

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Epidermolysis bullosa simplex

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.4

(source)

DANN

Benign

0.69

PhyloP100

0.38

PromoterAI

-0.0010

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over