Variant rs11551759 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.6C>T(p.Thr2Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 1,583,934 control chromosomes in the GnomAD database, including 275,896 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 25985 hom., cov: 32)

Exomes 𝑓: 0.58 ( 249911 hom. )

Consequence

KRT14
NM_000526.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.59

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=-0.56).

BP6

Variant 17-41586829-G-A is Benign according to our data. Variant chr17-41586829-G-A is described in ClinVar as [Benign]. Clinvar id is 256364.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-41586829-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=2.59 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	Protein	UniProt
KRT14	NM_000526.5 linkuse as main transcript	c.6C>T	p.Thr2Thr	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 linkuse as main transcript	c.6C>T	p.Thr2Thr	synonymous_variant	1/8	1	NM_000526.5	ENSP00000167586.6		P02533

Frequencies

GnomAD3 genomes

AF:

0.575

AC:

87347

AN:

151934

Hom.:

25969

Cov.:

show subpopulations

Gnomad AFR

AF:

0.473

Gnomad AMI

AF:

0.780

Gnomad AMR

AF:

0.678

Gnomad ASJ

AF:

0.558

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:

0.641

AC:

129973

AN:

202772

Hom.:

43294

AF XY:

0.637

AC XY:

70641

AN XY:

110890

show subpopulations

Gnomad AFR exome

AF:

0.461

Gnomad AMR exome

AF:

0.770

Gnomad ASJ exome

AF:

0.555

Gnomad EAS exome

AF:

0.943

Gnomad SAS exome

AF:

0.712

Gnomad FIN exome

AF:

0.661

Gnomad NFE exome

AF:

0.554

Gnomad OTH exome

AF:

0.589

GnomAD4 exome

AF:

0.584

AC:

836734

AN:

1431882

Hom.:

249911

Cov.:

AF XY:

0.587

AC XY:

417258

AN XY:

710308

show subpopulations

Gnomad4 AFR exome

AF:

0.471

Gnomad4 AMR exome

AF:

0.757

Gnomad4 ASJ exome

AF:

0.559

Gnomad4 EAS exome

AF:

0.959

Gnomad4 SAS exome

AF:

0.714

Gnomad4 FIN exome

AF:

0.664

Gnomad4 NFE exome

AF:

0.556

Gnomad4 OTH exome

AF:

0.584

GnomAD4 genome

AF:

0.575

AC:

87407

AN:

152052

Hom.:

25985

Cov.:

AF XY:

0.584

AC XY:

43393

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.472

Gnomad4 AMR

AF:

0.679

Gnomad4 ASJ

AF:

0.558

Gnomad4 EAS

AF:

0.949

Gnomad4 SAS

AF:

0.735

Gnomad4 FIN

AF:

0.659

Gnomad4 NFE

AF:

0.560

Gnomad4 OTH

AF:

0.565

Alfa

AF:

0.568

Hom.:

42373

Bravo

AF:

0.573

Asia WGS

AF:

0.822

AC:

2860

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.94

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