Variant 17-41395281-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_002277.3(KRT31):c.840C>T(p.Asn280Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00209 in 1,612,858 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 33 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 27 hom. )

Consequence

KRT31
NM_002277.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.70

Variant links:

Genes affected

KRT31 (HGNC:6448): (keratin 31) The protein encoded by this gene is a member of the keratin gene family. As a type I hair keratin, it is an acidic protein which heterodimerizes with type II keratins to form hair and nails. The type I hair keratins are clustered in a region of chromosome 17q12-q21 and have the same direction of transcription. [provided by RefSeq, Jul 2008]

KRT31 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 17-41395281-G-A is Benign according to our data. Variant chr17-41395281-G-A is described in ClinVar as [Benign]. Clinvar id is 777164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.7 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0107 (1631/152296) while in subpopulation AFR AF= 0.0369 (1532/41552). AF 95% confidence interval is 0.0353. There are 33 homozygotes in gnomad4. There are 764 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 33 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT31	NM_002277.3 linkuse as main transcript	c.840C>T	p.Asn280Asn	synonymous_variant	5/7	ENST00000251645.3	NP_002268.2	Q15323

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT31	ENST00000251645.3 linkuse as main transcript	c.840C>T	p.Asn280Asn	synonymous_variant	5/7	1	NM_002277.3	ENSP00000251645.2		Q15323

Frequencies

GnomAD3 genomes

AF:

0.0107

AC:

1622

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0368

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00353

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00623

GnomAD3 exomes

AF:

0.00248

AC:

623

AN:

251262

Hom.:

AF XY:

0.00196

AC XY:

266

AN XY:

135854

show subpopulations

Gnomad AFR exome

AF:

0.0334

Gnomad AMR exome

AF:

0.00127

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000621

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000158

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.00120

AC:

1746

AN:

1460562

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

772

AN XY:

726588

show subpopulations

Gnomad4 AFR exome

AF:

0.0387

Gnomad4 AMR exome

AF:

0.00157

Gnomad4 ASJ exome

AF:

0.000612

Gnomad4 EAS exome

AF:

0.000277

Gnomad4 SAS exome

AF:

0.00103

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000108

Gnomad4 OTH exome

AF:

0.00237

GnomAD4 genome

AF:

0.0107

AC:

1631

AN:

152296

Hom.:

Cov.:

AF XY:

0.0103

AC XY:

764

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0369

Gnomad4 AMR

AF:

0.00353

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00617

Alfa

AF:

0.00284

Hom.:

Bravo

AF:

0.0116

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

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 05, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.99

DANN

Benign

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