rs11551758

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000526.5(KRT14):c.189C>T(p.Cys63=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 151,994 control chromosomes in the GnomAD database, including 26,008 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.58 ( 26008 hom., cov: 32)

Exomes 𝑓: 0.59 ( 255401 hom. )

Failed GnomAD Quality Control

Consequence

KRT14
NM_000526.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3O:1

Conservation

PhyloP100: -2.51

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 17-41586646-G-A is Benign according to our data. Variant chr17-41586646-G-A is described in ClinVar as [Benign]. Clinvar id is 66331.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-41586646-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.51 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.927 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRT14	NM_000526.5 linkuse as main transcript	c.189C>T	p.Cys63=	synonymous_variant	1/8	ENST00000167586.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRT14	ENST00000167586.7 linkuse as main transcript	c.189C>T	p.Cys63=	synonymous_variant	1/8	1	NM_000526.5	P1

Frequencies

GnomAD3 genomes

AF:

0.575

AC:

87366

AN:

151876

Hom.:

25992

Cov.:

show subpopulations

Gnomad AFR

AF:

0.473

Gnomad AMI

AF:

0.780

Gnomad AMR

AF:

0.678

Gnomad ASJ

AF:

0.561

Gnomad EAS

AF:

0.949

Gnomad SAS

AF:

0.736

Gnomad FIN

AF:

0.659

Gnomad MID

AF:

0.440

Gnomad NFE

AF:

0.560

Gnomad OTH

AF:

0.561

GnomAD3 exomes

AF:

0.631

AC:

135116

AN:

214136

Hom.:

44582

AF XY:

0.629

AC XY:

73221

AN XY:

116470

show subpopulations

Gnomad AFR exome

AF:

0.453

Gnomad AMR exome

AF:

0.763

Gnomad ASJ exome

AF:

0.555

Gnomad EAS exome

AF:

0.942

Gnomad SAS exome

AF:

0.711

Gnomad FIN exome

AF:

0.657

Gnomad NFE exome

AF:

0.545

Gnomad OTH exome

AF:

0.587

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.586

AC:

851893

AN:

1453780

Hom.:

255401

Cov.:

AF XY:

0.589

AC XY:

425807

AN XY:

722740

show subpopulations

Gnomad4 AFR exome

AF:

0.472

Gnomad4 AMR exome

AF:

0.762

Gnomad4 ASJ exome

AF:

0.563

Gnomad4 EAS exome

AF:

0.959

Gnomad4 SAS exome

AF:

0.715

Gnomad4 FIN exome

AF:

0.664

Gnomad4 NFE exome

AF:

0.557

Gnomad4 OTH exome

AF:

0.585

GnomAD4 genome

AF:

0.575

AC:

87426

AN:

151994

Hom.:

26008

Cov.:

AF XY:

0.584

AC XY:

43401

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.473

Gnomad4 AMR

AF:

0.679

Gnomad4 ASJ

AF:

0.561

Gnomad4 EAS

AF:

0.949

Gnomad4 SAS

AF:

0.736

Gnomad4 FIN

AF:

0.659

Gnomad4 NFE

AF:

0.560

Gnomad4 OTH

AF:

0.565

Alfa

AF:

0.562

Hom.:

7681

Bravo

AF:

0.574

Asia WGS

AF:

0.823

AC:

2857

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:3Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1Other:1

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
not provided, no classification provided	literature only	Epithelial Biology; Institute of Medical Biology, Singapore	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Epidermolysis bullosa simplex 1A, generalized severe;C0080333:Epidermolysis bullosa simplex 1C, localized;C0343111:Naegeli-Franceschetti-Jadassohn syndrome;C0406778:Dermatopathia pigmentosa reticularis;C3715082:Epidermolysis bullosa simplex 1D, generalized, intermediate or severe, autosomal recessive;C5561924:Epidermolysis bullosa simplex, Koebner type

Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Aug 11, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

Cadd

Benign

0.95

Dann

Benign

0.56

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over