17-41518733-C-T

Position:

chr17-41518733-C-T

Variant summary

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

The ENST00000254043.8(KRT15):c.95G>A(p.Gly32Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000837 in 1,457,854 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict 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. G32R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0080 ( 22 hom., cov: 27)

Exomes 𝑓: 0.00084 ( 25 hom. )

Failed GnomAD Quality Control

Consequence

KRT15
ENST00000254043.8 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.918

Variant links:

Genes affected

KRT15 (HGNC:6421): (keratin 15) The protein encoded by this gene is a member of the keratin gene family. The keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells and are subdivided into cytokeratins and hair keratins. Most of the type I cytokeratins consist of acidic proteins which are arranged in pairs of heterotypic keratin chains and are clustered in a region on chromosome 17q21.2. [provided by RefSeq, Jul 2008]

KRT15 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=0.005801052).

BP6

Variant 17-41518733-C-T is Benign according to our data. Variant chr17-41518733-C-T is described in ClinVar as [Benign]. Clinvar id is 783781.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000837 (1220/1457854) while in subpopulation AFR AF= 0.0291 (967/33286). AF 95% confidence interval is 0.0275. There are 25 homozygotes in gnomad4_exome. There are 527 alleles in male gnomad4_exome subpopulation. Median coverage is 36. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
KRT15	NM_002275.4 linkuse as main transcript	c.95G>A	p.Gly32Glu	missense_variant	1/8	ENST00000254043.8	NP_002266.3
KRT15	XM_011524784.4 linkuse as main transcript	c.95G>A	p.Gly32Glu	missense_variant	1/8		XP_011523086.1
KRT15	XM_017024614.3 linkuse as main transcript	c.95G>A	p.Gly32Glu	missense_variant	1/8		XP_016880103.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT15	ENST00000254043.8 linkuse as main transcript	c.95G>A	p.Gly32Glu	missense_variant	1/8	1	NM_002275.4	ENSP00000254043	P1	P19012-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

1208

AN:

151154

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0282

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00276

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000738

Gnomad OTH

AF:

0.00241

GnomAD3 exomes

AF:

0.00226

AC:

559

AN:

247098

Hom.:

AF XY:

0.00172

AC XY:

230

AN XY:

133650

show subpopulations

Gnomad AFR exome

AF:

0.0303

Gnomad AMR exome

AF:

0.00165

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000665

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000448

Gnomad OTH exome

AF:

0.00151

GnomAD4 exome

AF:

0.000837

AC:

1220

AN:

1457854

Hom.:

Cov.:

AF XY:

0.000727

AC XY:

527

AN XY:

725300

show subpopulations

Gnomad4 AFR exome

AF:

0.0291

Gnomad4 AMR exome

AF:

0.00188

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000816

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000297

Gnomad4 OTH exome

AF:

0.00204

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00801

AC:

1212

AN:

151272

Hom.:

Cov.:

AF XY:

0.00783

AC XY:

579

AN XY:

73906

show subpopulations

Gnomad4 AFR

AF:

0.0282

Gnomad4 AMR

AF:

0.00276

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000738

Gnomad4 OTH

AF:

0.00239

Alfa

AF:

0.00130

Hom.:

Bravo

AF:

0.00922

ESP6500AA

AF:

0.0243

AC:

107

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00263

AC:

319

Asia WGS

AF:

0.00115

AC:

AN:

3478

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	Apr 16, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.16

T;T

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.30

.;T

MetaRNN

Benign

0.0058

T;T

MetaSVM

Benign

-0.55

MutationAssessor

Benign

1.8

L;L

MutationTaster

Benign

0.95

D;N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.21

Sift

Benign

0.042

D;D

Sift4G

Uncertain

0.024

D;D

Polyphen

0.43

B;B

Vest4

0.48

MVP

0.74

MPC

0.14

ClinPred

0.0049

GERP RS

3.5

Varity_R

0.12

gMVP

0.59

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