Variant rs8608 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_002273.4(KRT8):c.681A>G(p.Leu227Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 1,603,098 control chromosomes in the GnomAD database, including 226,251 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.50 ( 19461 hom., cov: 31)

Exomes 𝑓: 0.53 ( 206790 hom. )

Consequence

KRT8
NM_002273.4 synonymous

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 0.172

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP7

Synonymous conserved (PhyloP=0.172 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT8	NM_002273.4 link	c.681A>G	p.Leu227Leu	synonymous_variant	4/8	ENST00000692008.1	NP_002264.1	P05787-1
KRT8	NM_001256282.2 link	c.765A>G	p.Leu255Leu	synonymous_variant	5/9		NP_001243211.1	Q7L4M3
KRT8	NM_001256293.2 link	c.681A>G	p.Leu227Leu	synonymous_variant	5/9		NP_001243222.1	P05787-1
KRT8	NR_045962.2 link	n.1132A>G		non_coding_transcript_exon_variant	5/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT8	ENST00000692008.1 link	c.681A>G	p.Leu227Leu	synonymous_variant	4/8		NM_002273.4	ENSP00000509398.1		P05787-1

Frequencies

GnomAD3 genomes

AF:

0.502

AC:

76209

AN:

151788

Hom.:

19423

Cov.:

show subpopulations

Gnomad AFR

AF:

0.443

Gnomad AMI

AF:

0.616

Gnomad AMR

AF:

0.572

Gnomad ASJ

AF:

0.505

Gnomad EAS

AF:

0.624

Gnomad SAS

AF:

0.728

Gnomad FIN

AF:

0.413

Gnomad MID

AF:

0.585

Gnomad NFE

AF:

0.509

Gnomad OTH

AF:

0.507

GnomAD3 exomes

AF:

0.555

AC:

139593

AN:

251298

Hom.:

40251

AF XY:

0.558

AC XY:

75721

AN XY:

135820

show subpopulations

Gnomad AFR exome

AF:

0.441

Gnomad AMR exome

AF:

0.697

Gnomad ASJ exome

AF:

0.486

Gnomad EAS exome

AF:

0.625

Gnomad SAS exome

AF:

0.700

Gnomad FIN exome

AF:

0.421

Gnomad NFE exome

AF:

0.511

Gnomad OTH exome

AF:

0.533

GnomAD4 exome

AF:

0.529

AC:

767811

AN:

1451192

Hom.:

206790

Cov.:

AF XY:

0.533

AC XY:

385205

AN XY:

722404

show subpopulations

Gnomad4 AFR exome

AF:

0.446

Gnomad4 AMR exome

AF:

0.681

Gnomad4 ASJ exome

AF:

0.495

Gnomad4 EAS exome

AF:

0.636

Gnomad4 SAS exome

AF:

0.698

Gnomad4 FIN exome

AF:

0.425

Gnomad4 NFE exome

AF:

0.514

Gnomad4 OTH exome

AF:

0.530

GnomAD4 genome

AF:

0.502

AC:

76295

AN:

151906

Hom.:

19461

Cov.:

AF XY:

0.505

AC XY:

37510

AN XY:

74226

show subpopulations

Gnomad4 AFR

AF:

0.443

Gnomad4 AMR

AF:

0.573

Gnomad4 ASJ

AF:

0.505

Gnomad4 EAS

AF:

0.624

Gnomad4 SAS

AF:

0.729

Gnomad4 FIN

AF:

0.413

Gnomad4 NFE

AF:

0.509

Gnomad4 OTH

AF:

0.510

Alfa

AF:

0.513

Hom.:

14362

Bravo

AF:

0.513

Asia WGS

AF:

0.612

AC:

2128

AN:

3478

EpiCase

AF:

0.523

EpiControl

AF:

0.523

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

not provided

Other:1

not provided, no classification provided

literature only

Epithelial Biology; Institute of Medical Biology, Singapore

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

8.8

DANN

Benign

0.62

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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