Variant 17-40751196-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_181534.4(KRT25):c.800G>A(p.Arg267His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.019 in 1,614,118 control chromosomes in the GnomAD database, including 313 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R267C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.014 ( 16 hom., cov: 32)

Exomes 𝑓: 0.019 ( 297 hom. )

Consequence

KRT25
NM_181534.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.90

Variant links:

Genes affected

KRT25 (HGNC:30839): (keratin 25) This gene encodes a member of the type I (acidic) keratin family, which belongs to the superfamily of intermediate filament (IF) proteins. Keratins are heteropolymeric structural proteins which form the intermediate filament. These filaments, along with actin microfilaments and microtubules, compose the cytoskeleton of epithelial cells. The type I keratin genes are clustered in a region of chromosome 17q12-q21. [provided by RefSeq, Jul 2009]

KRT25 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008405983).

BP6

Variant 17-40751196-C-T is Benign according to our data. Variant chr17-40751196-C-T is described in ClinVar as [Benign]. Clinvar id is 2038746.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0144 (2188/152298) while in subpopulation NFE AF= 0.023 (1563/68012). AF 95% confidence interval is 0.022. There are 16 homozygotes in gnomad4. There are 1039 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRT25	NM_181534.4 linkuse as main transcript	c.800G>A	p.Arg267His	missense_variant	4/8	ENST00000312150.5
KRT25	XM_011524414.2 linkuse as main transcript	c.794G>A	p.Arg265His	missense_variant	5/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRT25	ENST00000312150.5 linkuse as main transcript	c.800G>A	p.Arg267His	missense_variant	4/8	1	NM_181534.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0144

AC:

2188

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00381

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0168

Gnomad ASJ

AF:

0.00663

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.0136

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0230

Gnomad OTH

AF:

0.0148

GnomAD3 exomes

AF:

0.0140

AC:

3525

AN:

251376

Hom.:

AF XY:

0.0137

AC XY:

1862

AN XY:

135850

show subpopulations

Gnomad AFR exome

AF:

0.00363

Gnomad AMR exome

AF:

0.00798

Gnomad ASJ exome

AF:

0.00585

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00167

Gnomad FIN exome

AF:

0.0128

Gnomad NFE exome

AF:

0.0238

Gnomad OTH exome

AF:

0.0152

GnomAD4 exome

AF:

0.0195

AC:

28473

AN:

1461820

Hom.:

297

Cov.:

AF XY:

0.0188

AC XY:

13695

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.00355

Gnomad4 AMR exome

AF:

0.00825

Gnomad4 ASJ exome

AF:

0.00497

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00169

Gnomad4 FIN exome

AF:

0.0157

Gnomad4 NFE exome

AF:

0.0233

Gnomad4 OTH exome

AF:

0.0158

GnomAD4 genome

AF:

0.0144

AC:

2188

AN:

152298

Hom.:

Cov.:

AF XY:

0.0140

AC XY:

1039

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00380

Gnomad4 AMR

AF:

0.0168

Gnomad4 ASJ

AF:

0.00663

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.0136

Gnomad4 NFE

AF:

0.0230

Gnomad4 OTH

AF:

0.0147

Alfa

AF:

0.0186

Hom.:

Bravo

AF:

0.0140

TwinsUK

AF:

0.0270

AC:

100

ALSPAC

AF:

0.0205

AC:

ESP6500AA

AF:

0.00590

AC:

ESP6500EA

AF:

0.0197

AC:

169

ExAC

AF:

0.0147

AC:

1787

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0183

EpiControl

AF:

0.0192

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 08, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Pathogenic

0.83

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.90

MetaRNN

Benign

0.0084

MetaSVM

Uncertain

0.32

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-3.8

REVEL

Uncertain

0.53

Sift

Benign

0.033

Sift4G

Uncertain

0.010

Polyphen

0.94

Vest4

0.21

MPC

0.19

ClinPred

0.029

GERP RS

5.8

Varity_R

0.31

gMVP

0.89

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