rs11554495

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_002273.4(KRT8):c.184G>T(p.Gly62Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00816 in 1,612,350 control chromosomes in the GnomAD database, including 75 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0052 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0085 ( 70 hom. )

Consequence

KRT8
NM_002273.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1B:5O:1

Conservation

PhyloP100: 0.761

Publications

49 publications found

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 Gene-Disease associations (from GenCC):

cirrhosis, familial
Inheritance: AR, Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

KRT8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.030593991).

BP6

Variant 12-52904798-C-A is Benign according to our data. Variant chr12-52904798-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 14630.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002273.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KRT8	NM_002273.4	MANE Select	c.184G>T	p.Gly62Cys	missense	Exon 1 of 8	NP_002264.1	P05787-1
KRT8	NM_001256282.2		c.268G>T	p.Gly90Cys	missense	Exon 2 of 9	NP_001243211.1	P05787-2
KRT8	NM_001256293.2		c.184G>T	p.Gly62Cys	missense	Exon 2 of 9	NP_001243222.1	P05787-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KRT8	ENST00000692008.1	MANE Select	c.184G>T	p.Gly62Cys	missense	Exon 1 of 8	ENSP00000509398.1	P05787-1
KRT8	ENST00000552150.5	TSL:1	c.268G>T	p.Gly90Cys	missense	Exon 2 of 9	ENSP00000449404.1	P05787-2
KRT8	ENST00000871797.1		c.184G>T	p.Gly62Cys	missense	Exon 1 of 8	ENSP00000541856.1

Frequencies

GnomAD3 genomes

AF:

0.00518

AC:

788

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00200

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00969

Gnomad OTH

AF:

0.00382

GnomAD2 exomes

AF:

0.00485

AC:

1209

AN:

249256

AF XY:

0.00499

show subpopulations

Gnomad AFR exome

AF:

0.00147

Gnomad AMR exome

AF:

0.00171

Gnomad ASJ exome

AF:

0.000500

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00129

Gnomad NFE exome

AF:

0.00932

Gnomad OTH exome

AF:

0.00525

GnomAD4 exome

AF:

0.00847

AC:

12373

AN:

1460024

Hom.:

Cov.:

AF XY:

0.00822

AC XY:

5972

AN XY:

726348

show subpopulations

African (AFR)

AF:

0.00135

AC:

AN:

33438

American (AMR)

AF:

0.00179

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.000344

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000801

AC:

AN:

86172

European-Finnish (FIN)

AF:

0.00171

AC:

AN:

52782

Middle Eastern (MID)

AF:

0.00185

AC:

AN:

4868

European-Non Finnish (NFE)

AF:

0.0106

AC:

11763

AN:

1111928

Other (OTH)

AF:

0.00511

AC:

308

AN:

60294

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

727

1454

2182

2909

3636

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

446

892

1338

1784

2230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00517

AC:

788

AN:

152326

Hom.:

Cov.:

AF XY:

0.00432

AC XY:

322

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.00200

AC:

AN:

41580

American (AMR)

AF:

0.00163

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000829

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.000659

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00969

AC:

659

AN:

68020

Other (OTH)

AF:

0.00378

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

109

146

182

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00500

Hom.:

Bravo

AF:

0.00503

TwinsUK

AF:

0.00998

AC:

ALSPAC

AF:

0.0127

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00687

AC:

ExAC

AF:

0.00505

AC:

613

EpiCase

AF:

0.00796

EpiControl

AF:

0.00818

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (5)

Cirrhosis, cryptogenic (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Uncertain

0.030

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.71

Eigen

Benign

0.0040

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.60

M_CAP

Pathogenic

0.67

MetaRNN

Benign

0.031

MetaSVM

Uncertain

0.57

MutationAssessor

Pathogenic

3.3

PhyloP100

0.76

PrimateAI

Benign

0.35

PROVEAN

Pathogenic

-6.2

REVEL

Uncertain

0.53

Sift

Uncertain

0.0020

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.30

MVP

0.95

MPC

1.4

ClinPred

0.11

GERP RS

1.7

PromoterAI

-0.058

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.56

gMVP

0.93

Mutation Taster

=76/24

disease causing (ClinVar)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over