Variant chr17-40750466-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_181534.4(KRT25):c.1089G>A(p.Lys363=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0111 in 1,614,038 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0085 ( 7 hom., cov: 32)

Exomes 𝑓: 0.011 ( 107 hom. )

Consequence

KRT25
NM_181534.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.37

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 17-40750466-C-T is Benign according to our data. Variant chr17-40750466-C-T is described in ClinVar as [Benign]. Clinvar id is 708240.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.37 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRT25	NM_181534.4 linkuse as main transcript	c.1089G>A	p.Lys363=	synonymous_variant	6/8	ENST00000312150.5
KRT25	XM_011524414.2 linkuse as main transcript	c.1083G>A	p.Lys361=	synonymous_variant	7/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRT25	ENST00000312150.5 linkuse as main transcript	c.1089G>A	p.Lys363=	synonymous_variant	6/8	1	NM_181534.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00851

AC:

1295

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00224

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00563

Gnomad ASJ

AF:

0.0159

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00600

Gnomad FIN

AF:

0.0104

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0131

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.00965

AC:

2425

AN:

251286

Hom.:

AF XY:

0.0102

AC XY:

1383

AN XY:

135804

show subpopulations

Gnomad AFR exome

AF:

0.00271

Gnomad AMR exome

AF:

0.00610

Gnomad ASJ exome

AF:

0.0176

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00676

Gnomad FIN exome

AF:

0.0111

Gnomad NFE exome

AF:

0.0131

Gnomad OTH exome

AF:

0.00946

GnomAD4 exome

AF:

0.0114

AC:

16598

AN:

1461758

Hom.:

107

Cov.:

AF XY:

0.0113

AC XY:

8240

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.00176

Gnomad4 AMR exome

AF:

0.00602

Gnomad4 ASJ exome

AF:

0.0178

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00729

Gnomad4 FIN exome

AF:

0.0102

Gnomad4 NFE exome

AF:

0.0125

Gnomad4 OTH exome

AF:

0.0108

GnomAD4 genome

AF:

0.00850

AC:

1294

AN:

152280

Hom.:

Cov.:

AF XY:

0.00803

AC XY:

598

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00224

Gnomad4 AMR

AF:

0.00562

Gnomad4 ASJ

AF:

0.0159

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00601

Gnomad4 FIN

AF:

0.0104

Gnomad4 NFE

AF:

0.0131

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.0123

Hom.:

Bravo

AF:

0.00822

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0141

EpiControl

AF:

0.0135

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	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2023	KRT25: BP4, BP7, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 21, 2023	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

2.4

DANN

Benign

0.49

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