17-41583206-G-C

Variant names:

Variant summary

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

The NM_000526.5(KRT14):c.1274+29C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0311 in 1,613,036 control chromosomes in the GnomAD database, including 1,812 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 157 hom., cov: 32)

Exomes 𝑓: 0.032 ( 1655 hom. )

Consequence

KRT14
NM_000526.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.58

Publications

4 publications found

Variant links:

Genes affected

KRT14 (HGNC:6416): (keratin 14) This gene encodes a member of the keratin family, the most diverse group of intermediate filaments. This gene product, a type I keratin, is usually found as a heterotetramer with two keratin 5 molecules, a type II keratin. Together they form the cytoskeleton of epithelial cells. Mutations in the genes for these keratins are associated with epidermolysis bullosa simplex. At least one pseudogene has been identified at 17p12-p11. [provided by RefSeq, Jul 2008]

KRT14 Gene-Disease associations (from GenCC):

epidermolysis bullosa simplex 1A, generalized severe
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Ambry Genetics, Orphanet
Naegeli-Franceschetti-Jadassohn syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P, Genomics England PanelApp
epidermolysis bullosa simplex
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
epidermolysis bullosa simplex 1D, generalized, intermediate or severe, autosomal recessive
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet
dermatopathia pigmentosa reticularis
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp
epidermolysis bullosa simplex 1B, generalized intermediate
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
epidermolysis bullosa simplex 1C, localized
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp
epidermolysis bullosa simplex 2F, with mottled pigmentation
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

KRT14 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=-0.85).

BP6

Variant 17-41583206-G-C is Benign according to our data. Variant chr17-41583206-G-C is described in ClinVar as Benign. ClinVar VariationId is 1271599.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000526.5. 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
	KRT14	NM_000526.5	MANE Select	c.1274+29C>G		intron	N/A	NP_000517.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KRT14	ENST00000167586.7	TSL:1 MANE Select	c.1274+29C>G	intron	N/A	ENSP00000167586.6	P02533
KRT14	ENST00000441550.2	TSL:2	n.221+29C>G	intron	N/A
KRT14	ENST00000476662.1	TSL:2	n.*43C>G	downstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.0254

AC:

3861

AN:

152032

Hom.:

157

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00556

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.0195

Gnomad ASJ

AF:

0.0588

Gnomad EAS

AF:

0.168

Gnomad SAS

AF:

0.124

Gnomad FIN

AF:

0.00961

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0217

Gnomad OTH

AF:

0.0311

GnomAD2 exomes

AF:

0.0439

AC:

11008

AN:

250964

AF XY:

0.0478

show subpopulations

Gnomad AFR exome

AF:

0.00552

Gnomad AMR exome

AF:

0.0135

Gnomad ASJ exome

AF:

0.0595

Gnomad EAS exome

AF:

0.175

Gnomad FIN exome

AF:

0.0108

Gnomad NFE exome

AF:

0.0222

Gnomad OTH exome

AF:

0.0368

GnomAD4 exome

AF:

0.0317

AC:

46308

AN:

1460886

Hom.:

1655

Cov.:

AF XY:

0.0344

AC XY:

25017

AN XY:

726760

show subpopulations

African (AFR)

AF:

0.00521

AC:

174

AN:

33428

American (AMR)

AF:

0.0148

AC:

664

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0589

AC:

1540

AN:

26132

East Asian (EAS)

AF:

0.153

AC:

6073

AN:

39694

South Asian (SAS)

AF:

0.118

AC:

10145

AN:

86210

European-Finnish (FIN)

AF:

0.0106

AC:

568

AN:

53418

Middle Eastern (MID)

AF:

0.0588

AC:

312

AN:

5306

European-Non Finnish (NFE)

AF:

0.0219

AC:

24308

AN:

1111636

Other (OTH)

AF:

0.0418

AC:

2524

AN:

60338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.527

Heterozygous variant carriers

3020

6039

9059

12078

15098

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1090

2180

3270

4360

5450

<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:

0.0254

AC:

3864

AN:

152150

Hom.:

157

Cov.:

AF XY:

0.0265

AC XY:

1968

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.00559

AC:

232

AN:

41488

American (AMR)

AF:

0.0195

AC:

298

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0588

AC:

204

AN:

3470

East Asian (EAS)

AF:

0.168

AC:

865

AN:

5144

South Asian (SAS)

AF:

0.125

AC:

601

AN:

4822

European-Finnish (FIN)

AF:

0.00961

AC:

102

AN:

10612

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0217

AC:

1473

AN:

67994

Other (OTH)

AF:

0.0313

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

186

371

557

742

928

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

186

248

310

<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:

0.0156

Hom.:

Bravo

AF:

0.0241

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.50

(source)

DANN

Benign

0.48

PhyloP100

-1.6

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