Variant 17-41582500-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000526.5(KRT14):c.1354G>A(p.Val452Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.02 in 1,572,222 control chromosomes in the GnomAD database, including 383 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 29 hom., cov: 32)

Exomes 𝑓: 0.020 ( 354 hom. )

Consequence

KRT14
NM_000526.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.710

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002311796).

BP6

Variant 17-41582500-C-T is Benign according to our data. Variant chr17-41582500-C-T is described in ClinVar as [Benign]. Clinvar id is 1537948.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0168 (2552/152262) while in subpopulation NFE AF= 0.0232 (1576/68020). AF 95% confidence interval is 0.0222. There are 29 homozygotes in gnomad4. There are 1319 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 29 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT14	NM_000526.5 link	c.1354G>A	p.Val452Ile	missense_variant	8/8	ENST00000167586.7	NP_000517.3	P02533

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT14	ENST00000167586.7 link	c.1354G>A	p.Val452Ile	missense_variant	8/8	1	NM_000526.5	ENSP00000167586.6		P02533
KRT14	ENST00000441550.2 link	n.862G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.0168

AC:

2553

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00372

Gnomad AMI

AF:

0.00440

Gnomad AMR

AF:

0.0154

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.0496

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0232

Gnomad OTH

AF:

0.0139

GnomAD3 exomes

AF:

0.0164

AC:

3033

AN:

184884

Hom.:

AF XY:

0.0158

AC XY:

1560

AN XY:

98470

show subpopulations

Gnomad AFR exome

AF:

0.00402

Gnomad AMR exome

AF:

0.0119

Gnomad ASJ exome

AF:

0.00407

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00179

Gnomad FIN exome

AF:

0.0463

Gnomad NFE exome

AF:

0.0221

Gnomad OTH exome

AF:

0.0167

GnomAD4 exome

AF:

0.0203

AC:

28842

AN:

1419960

Hom.:

354

Cov.:

AF XY:

0.0197

AC XY:

13841

AN XY:

702314

show subpopulations

Gnomad4 AFR exome

AF:

0.00308

Gnomad4 AMR exome

AF:

0.0122

Gnomad4 ASJ exome

AF:

0.00434

Gnomad4 EAS exome

AF:

0.0000802

Gnomad4 SAS exome

AF:

0.00207

Gnomad4 FIN exome

AF:

0.0458

Gnomad4 NFE exome

AF:

0.0227

Gnomad4 OTH exome

AF:

0.0156

GnomAD4 genome

AF:

0.0168

AC:

2552

AN:

152262

Hom.:

Cov.:

AF XY:

0.0177

AC XY:

1319

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.00371

Gnomad4 AMR

AF:

0.0154

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.0496

Gnomad4 NFE

AF:

0.0232

Gnomad4 OTH

AF:

0.0137

Alfa

AF:

0.0161

Hom.:

Bravo

AF:

0.0138

TwinsUK

AF:

0.0227

AC:

ALSPAC

AF:

0.0208

AC:

ESP6500AA

AF:

0.00568

AC:

ESP6500EA

AF:

0.0221

AC:

190

ExAC

AF:

0.0113

AC:

1343

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 21, 2025	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.041

Eigen

Benign

0.083

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.46

MetaRNN

Benign

0.0023

MetaSVM

Benign

-0.31

MutationAssessor

Benign

1.7

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.30

REVEL

Benign

0.28

Sift

Benign

0.13

Sift4G

Benign

0.16

Polyphen

0.10

Vest4

0.063

MPC

0.54

ClinPred

0.053

GERP RS

5.4

Varity_R

0.098

gMVP

0.93

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