NM_000424.4:c.*253C>T

Variant names:

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.*253C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 490,176 control chromosomes in the GnomAD database, including 4,753 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 1797 hom., cov: 32)

Exomes 𝑓: 0.12 ( 2956 hom. )

Consequence

KRT5
NM_000424.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.171

Publications

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

KRT5 links:

ENSG00000303382 (HGNC:):

ENSG00000303382 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=-0.86).

BP6

Variant 12-52514689-G-A is Benign according to our data. Variant chr12-52514689-G-A is described in ClinVar as Benign. ClinVar VariationId is 309550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000424.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT5	NM_000424.4	MANE Select	c.*253C>T		3_prime_UTR	Exon 9 of 9	NP_000415.2	P13647

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KRT5	ENST00000252242.9	TSL:1 MANE Select	c.*253C>T	3_prime_UTR	Exon 9 of 9	ENSP00000252242.4	P13647
ENSG00000303382	ENST00000794060.1		n.465-1891G>A	intron	N/A
ENSG00000303382	ENST00000794061.1		n.380+17261G>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.150

AC:

22811

AN:

151990

Hom.:

1791

Cov.:

show subpopulations

Gnomad AFR

AF:

0.179

Gnomad AMI

AF:

0.270

Gnomad AMR

AF:

0.178

Gnomad ASJ

AF:

0.198

Gnomad EAS

AF:

0.0337

Gnomad SAS

AF:

0.101

Gnomad FIN

AF:

0.125

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.137

Gnomad OTH

AF:

0.181

GnomAD4 exome

AF:

0.122

AC:

41236

AN:

338068

Hom.:

2956

Cov.:

AF XY:

0.120

AC XY:

20796

AN XY:

173386

show subpopulations

African (AFR)

AF:

0.173

AC:

1833

AN:

10578

American (AMR)

AF:

0.157

AC:

1951

AN:

12408

Ashkenazi Jewish (ASJ)

AF:

0.186

AC:

2100

AN:

11298

East Asian (EAS)

AF:

0.0208

AC:

560

AN:

26916

South Asian (SAS)

AF:

0.0796

AC:

1597

AN:

20058

European-Finnish (FIN)

AF:

0.123

AC:

2959

AN:

24014

Middle Eastern (MID)

AF:

0.164

AC:

267

AN:

1630

European-Non Finnish (NFE)

AF:

0.129

AC:

27077

AN:

210146

Other (OTH)

AF:

0.138

AC:

2892

AN:

21020

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

1627

3254

4881

6508

8135

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

172

344

516

688

860

<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:

0.150

AC:

22842

AN:

152108

Hom.:

1797

Cov.:

AF XY:

0.150

AC XY:

11155

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.179

AC:

7429

AN:

41470

American (AMR)

AF:

0.178

AC:

2719

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.198

AC:

686

AN:

3468

East Asian (EAS)

AF:

0.0333

AC:

173

AN:

5188

South Asian (SAS)

AF:

0.101

AC:

486

AN:

4800

European-Finnish (FIN)

AF:

0.125

AC:

1325

AN:

10584

Middle Eastern (MID)

AF:

0.211

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.137

AC:

9340

AN:

67998

Other (OTH)

AF:

0.178

AC:

376

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

970

1940

2911

3881

4851

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

242

484

726

968

1210

<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:

0.144

Hom.:

1574

Bravo

AF:

0.154

Asia WGS

AF:

0.0900

AC:

314

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Epidermolysis bullosa simplex (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.6

(source)

DANN

Benign

0.67

PhyloP100

-0.17

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over