Variant rs13098 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The ENST00000552150.5(KRT8):c.75T>A(p.Pro25=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 1,602,140 control chromosomes in the GnomAD database, including 9,264 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.082 ( 715 hom., cov: 32)

Exomes 𝑓: 0.10 ( 8549 hom. )

Consequence

KRT8
ENST00000552150.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.345

Variant links:

Genes affected

KRT8 (HGNC:6446): (keratin 8) This gene is a member of the type II keratin family clustered on the long arm of chromosome 12. Type I and type II keratins heteropolymerize to form intermediate-sized filaments in the cytoplasm of epithelial cells. The product of this gene typically dimerizes with keratin 18 to form an intermediate filament in simple single-layered epithelial cells. This protein plays a role in maintaining cellular structural integrity and also functions in signal transduction and cellular differentiation. Mutations in this gene cause cryptogenic cirrhosis. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2012]

KRT8 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 12-52904991-A-T is Benign according to our data. Variant chr12-52904991-A-T is described in ClinVar as [Benign]. Clinvar id is 3057189.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.345 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
KRT8	NM_002273.4 linkuse as main transcript	c.-10T>A		5_prime_UTR_variant	1/8	ENST00000692008.1
KRT8	NM_001256282.2 linkuse as main transcript	c.75T>A	p.Pro25=	synonymous_variant	2/9
KRT8	NM_001256293.2 linkuse as main transcript	c.-10T>A		5_prime_UTR_variant	2/9
KRT8	NR_045962.2 linkuse as main transcript	n.442T>A		non_coding_transcript_exon_variant	2/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRT8	ENST00000692008.1 linkuse as main transcript	c.-10T>A		5_prime_UTR_variant	1/8		NM_002273.4	P2	P05787-1

Frequencies

GnomAD3 genomes

AF:

0.0826

AC:

12562

AN:

152128

Hom.:

716

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0194

Gnomad AMI

AF:

0.158

Gnomad AMR

AF:

0.0661

Gnomad ASJ

AF:

0.162

Gnomad EAS

AF:

0.000579

Gnomad SAS

AF:

0.0403

Gnomad FIN

AF:

0.150

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.118

Gnomad OTH

AF:

0.0900

GnomAD3 exomes

AF:

0.0901

AC:

20783

AN:

230758

Hom.:

1198

AF XY:

0.0918

AC XY:

11672

AN XY:

127210

show subpopulations

Gnomad AFR exome

AF:

0.0152

Gnomad AMR exome

AF:

0.0448

Gnomad ASJ exome

AF:

0.163

Gnomad EAS exome

AF:

0.000339

Gnomad SAS exome

AF:

0.0457

Gnomad FIN exome

AF:

0.152

Gnomad NFE exome

AF:

0.125

Gnomad OTH exome

AF:

0.0960

GnomAD4 exome

AF:

0.104

AC:

151461

AN:

1449894

Hom.:

8549

Cov.:

AF XY:

0.104

AC XY:

74879

AN XY:

720926

show subpopulations

Gnomad4 AFR exome

AF:

0.0162

Gnomad4 AMR exome

AF:

0.0453

Gnomad4 ASJ exome

AF:

0.155

Gnomad4 EAS exome

AF:

0.000430

Gnomad4 SAS exome

AF:

0.0478

Gnomad4 FIN exome

AF:

0.150

Gnomad4 NFE exome

AF:

0.115

Gnomad4 OTH exome

AF:

0.0926

GnomAD4 genome

AF:

0.0825

AC:

12558

AN:

152246

Hom.:

715

Cov.:

AF XY:

0.0817

AC XY:

6079

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0193

Gnomad4 AMR

AF:

0.0661

Gnomad4 ASJ

AF:

0.162

Gnomad4 EAS

AF:

0.000581

Gnomad4 SAS

AF:

0.0406

Gnomad4 FIN

AF:

0.150

Gnomad4 NFE

AF:

0.118

Gnomad4 OTH

AF:

0.0890

Alfa

AF:

0.106

Hom.:

182

Bravo

AF:

0.0730

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

KRT8-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 12, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

DANN

Benign

0.68

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