Variant 17-40749225-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_181534.4(KRT25):c.1243+33A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 1,513,698 control chromosomes in the GnomAD database, including 168,374 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 16116 hom., cov: 32)

Exomes 𝑓: 0.47 ( 152258 hom. )

Consequence

KRT25
NM_181534.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.18

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 17-40749225-T-G is Benign according to our data. Variant chr17-40749225-T-G is described in ClinVar as [Benign]. Clinvar id is 1225872.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRT25	NM_181534.4 linkuse as main transcript	c.1243+33A>C		intron_variant		ENST00000312150.5
KRT25	XM_011524414.2 linkuse as main transcript	c.1237+33A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRT25	ENST00000312150.5 linkuse as main transcript	c.1243+33A>C		intron_variant		1	NM_181534.4	P1

Frequencies

GnomAD3 genomes

AF:

0.456

AC:

69244

AN:

151886

Hom.:

16112

Cov.:

show subpopulations

Gnomad AFR

AF:

0.403

Gnomad AMI

AF:

0.484

Gnomad AMR

AF:

0.399

Gnomad ASJ

AF:

0.482

Gnomad EAS

AF:

0.704

Gnomad SAS

AF:

0.525

Gnomad FIN

AF:

0.502

Gnomad MID

AF:

0.358

Gnomad NFE

AF:

0.468

Gnomad OTH

AF:

0.461

GnomAD3 exomes

AF:

0.486

AC:

119597

AN:

246292

Hom.:

29918

AF XY:

0.487

AC XY:

64790

AN XY:

133142

show subpopulations

Gnomad AFR exome

AF:

0.405

Gnomad AMR exome

AF:

0.414

Gnomad ASJ exome

AF:

0.478

Gnomad EAS exome

AF:

0.735

Gnomad SAS exome

AF:

0.503

Gnomad FIN exome

AF:

0.507

Gnomad NFE exome

AF:

0.472

Gnomad OTH exome

AF:

0.461

GnomAD4 exome

AF:

0.469

AC:

638613

AN:

1361692

Hom.:

152258

Cov.:

AF XY:

0.470

AC XY:

320726

AN XY:

682676

show subpopulations

Gnomad4 AFR exome

AF:

0.389

Gnomad4 AMR exome

AF:

0.410

Gnomad4 ASJ exome

AF:

0.481

Gnomad4 EAS exome

AF:

0.688

Gnomad4 SAS exome

AF:

0.502

Gnomad4 FIN exome

AF:

0.504

Gnomad4 NFE exome

AF:

0.461

Gnomad4 OTH exome

AF:

0.471

GnomAD4 genome

AF:

0.456

AC:

69277

AN:

152006

Hom.:

16116

Cov.:

AF XY:

0.456

AC XY:

33910

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.403

Gnomad4 AMR

AF:

0.398

Gnomad4 ASJ

AF:

0.482

Gnomad4 EAS

AF:

0.704

Gnomad4 SAS

AF:

0.525

Gnomad4 FIN

AF:

0.502

Gnomad4 NFE

AF:

0.468

Gnomad4 OTH

AF:

0.465

Alfa

AF:

0.457

Hom.:

17152

Bravo

AF:

0.446

Asia WGS

AF:

0.575

AC:

1999

AN:

3478

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

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.59

DANN

Benign

0.35

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