Variant rs3826549 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000526.5(KRT14):c.369T>C(p.Asn123Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 1,613,754 control chromosomes in the GnomAD database, including 283,068 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 25950 hom., cov: 31)

Exomes 𝑓: 0.59 ( 257118 hom. )

Consequence

KRT14
NM_000526.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5O:1

Conservation

PhyloP100: -0.276

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=-0.69).

BP6

Variant 17-41586466-A-G is Benign according to our data. Variant chr17-41586466-A-G is described in ClinVar as [Benign]. Clinvar id is 66346.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-41586466-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.276 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT14	NM_000526.5 link	c.369T>C	p.Asn123Asn	synonymous_variant	1/8	ENST00000167586.7	NP_000517.3	P02533

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT14	ENST00000167586.7 link	c.369T>C	p.Asn123Asn	synonymous_variant	1/8	1	NM_000526.5	ENSP00000167586.6		P02533

Frequencies

GnomAD3 genomes

AF:

0.575

AC:

87247

AN:

151762

Hom.:

25934

Cov.:

show subpopulations

Gnomad AFR

AF:

0.473

Gnomad AMI

AF:

0.780

Gnomad AMR

AF:

0.676

Gnomad ASJ

AF:

0.562

Gnomad EAS

AF:

0.948

Gnomad SAS

AF:

0.736

Gnomad FIN

AF:

0.658

Gnomad MID

AF:

0.437

Gnomad NFE

AF:

0.560

Gnomad OTH

AF:

0.560

GnomAD3 exomes

AF:

0.644

AC:

161967

AN:

251458

Hom.:

54299

AF XY:

0.641

AC XY:

87143

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.476

Gnomad AMR exome

AF:

0.777

Gnomad ASJ exome

AF:

0.561

Gnomad EAS exome

AF:

0.945

Gnomad SAS exome

AF:

0.718

Gnomad FIN exome

AF:

0.666

Gnomad NFE exome

AF:

0.565

Gnomad OTH exome

AF:

0.596

GnomAD4 exome

AF:

0.586

AC:

857284

AN:

1461874

Hom.:

257118

Cov.:

AF XY:

0.590

AC XY:

428742

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.472

Gnomad4 AMR exome

AF:

0.764

Gnomad4 ASJ exome

AF:

0.563

Gnomad4 EAS exome

AF:

0.959

Gnomad4 SAS exome

AF:

0.716

Gnomad4 FIN exome

AF:

0.665

Gnomad4 NFE exome

AF:

0.557

Gnomad4 OTH exome

AF:

0.585

GnomAD4 genome

AF:

0.575

AC:

87307

AN:

151880

Hom.:

25950

Cov.:

AF XY:

0.584

AC XY:

43331

AN XY:

74242

show subpopulations

Gnomad4 AFR

AF:

0.473

Gnomad4 AMR

AF:

0.677

Gnomad4 ASJ

AF:

0.562

Gnomad4 EAS

AF:

0.948

Gnomad4 SAS

AF:

0.735

Gnomad4 FIN

AF:

0.658

Gnomad4 NFE

AF:

0.560

Gnomad4 OTH

AF:

0.564

Alfa

AF:

0.557

Hom.:

10161

Bravo

AF:

0.573

EpiCase

AF:

0.547

EpiControl

AF:

0.556

ClinVar

Significance: Benign

Submissions summary: Benign:5Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3Other:1

not provided, no classification provided	literature only	Epithelial Biology; Institute of Medical Biology, Singapore	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

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

-0.69

CADD

Benign

6.8

DANN

Benign

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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