Variant rs6503639 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.231C>T(p.Ser77=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 1,612,034 control chromosomes in the GnomAD database, including 76,091 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5341 hom., cov: 33)

Exomes 𝑓: 0.30 ( 70750 hom. )

Consequence

KRT14
NM_000526.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: -0.432

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=-0.63).

BP6

Variant 17-41586604-G-A is Benign according to our data. Variant chr17-41586604-G-A is described in ClinVar as [Benign]. Clinvar id is 66334.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-41586604-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.432 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.328 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.231C>T	p.Ser77=	synonymous_variant	1/8	ENST00000167586.7	NP_000517.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT14	ENST00000167586.7 linkuse as main transcript	c.231C>T	p.Ser77=	synonymous_variant	1/8	1	NM_000526.5	ENSP00000167586	P1

Frequencies

GnomAD3 genomes

AF:

0.252

AC:

38288

AN:

151686

Hom.:

5341

Cov.:

show subpopulations

Gnomad AFR

AF:

0.168

Gnomad AMI

AF:

0.188

Gnomad AMR

AF:

0.226

Gnomad ASJ

AF:

0.289

Gnomad EAS

AF:

0.00270

Gnomad SAS

AF:

0.141

Gnomad FIN

AF:

0.270

Gnomad MID

AF:

0.326

Gnomad NFE

AF:

0.331

Gnomad OTH

AF:

0.273

GnomAD3 exomes

AF:

0.241

AC:

58761

AN:

243662

Hom.:

8297

AF XY:

0.245

AC XY:

32373

AN XY:

132320

show subpopulations

Gnomad AFR exome

AF:

0.166

Gnomad AMR exome

AF:

0.156

Gnomad ASJ exome

AF:

0.289

Gnomad EAS exome

AF:

0.000390

Gnomad SAS exome

AF:

0.153

Gnomad FIN exome

AF:

0.268

Gnomad NFE exome

AF:

0.331

Gnomad OTH exome

AF:

0.275

GnomAD4 exome

AF:

0.301

AC:

439824

AN:

1460230

Hom.:

70750

Cov.:

103

AF XY:

0.298

AC XY:

216096

AN XY:

726336

show subpopulations

Gnomad4 AFR exome

AF:

0.160

Gnomad4 AMR exome

AF:

0.163

Gnomad4 ASJ exome

AF:

0.286

Gnomad4 EAS exome

AF:

0.000630

Gnomad4 SAS exome

AF:

0.157

Gnomad4 FIN exome

AF:

0.272

Gnomad4 NFE exome

AF:

0.336

Gnomad4 OTH exome

AF:

0.284

GnomAD4 genome

AF:

0.252

AC:

38297

AN:

151804

Hom.:

5341

Cov.:

AF XY:

0.247

AC XY:

18311

AN XY:

74216

show subpopulations

Gnomad4 AFR

AF:

0.168

Gnomad4 AMR

AF:

0.226

Gnomad4 ASJ

AF:

0.289

Gnomad4 EAS

AF:

0.00270

Gnomad4 SAS

AF:

0.141

Gnomad4 FIN

AF:

0.270

Gnomad4 NFE

AF:

0.331

Gnomad4 OTH

AF:

0.270

Alfa

AF:

0.305

Hom.:

2360

Bravo

AF:

0.242

Asia WGS

AF:

0.0820

AC:

285

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3Other:1

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
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	-	- -

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

-0.63

CADD

Benign

7.2

DANN

Benign

0.54

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