Variant chr12-52949347-G-GA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_000224.3(KRT18):c.174_175insA(p.Gly59ArgfsTer97) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.36 ( 0 hom., cov: 37)

Exomes 𝑓: 0.000073 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KRT18
NM_000224.3 frameshift

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.45

Variant links:

Genes affected

KRT18 (HGNC:6430): (keratin 18) KRT18 encodes the type I intermediate filament chain keratin 18. Keratin 18, together with its filament partner keratin 8, are perhaps the most commonly found members of the intermediate filament gene family. They are expressed in single layer epithelial tissues of the body. Mutations in this gene have been linked to cryptogenic cirrhosis. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

KRT18 links:

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 Likely_benign. Variant got -2 ACMG points.

BP6

Variant 12-52949347-G-GA is Benign according to our data. Variant chr12-52949347-G-GA is described in ClinVar as [Benign]. Clinvar id is 1301593.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
KRT18	NM_000224.3 linkuse as main transcript	c.174_175insA	p.Gly59ArgfsTer97	frameshift_variant	1/7	ENST00000388835.4
KRT18	NM_199187.2 linkuse as main transcript	c.174_175insA	p.Gly59ArgfsTer97	frameshift_variant	2/8
KRT8	NM_001256293.2 linkuse as main transcript	c.-47+367_-47+368insT		intron_variant
KRT8	NR_045962.2 linkuse as main transcript	n.405+108_405+109insT		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRT18	ENST00000388835.4 linkuse as main transcript	c.174_175insA	p.Gly59ArgfsTer97	frameshift_variant	1/7	1	NM_000224.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

27412

AN:

75740

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.356

Gnomad AMI

AF:

0.441

Gnomad AMR

AF:

0.349

Gnomad ASJ

AF:

0.395

Gnomad EAS

AF:

0.275

Gnomad SAS

AF:

0.303

Gnomad FIN

AF:

0.336

Gnomad MID

AF:

0.148

Gnomad NFE

AF:

0.385

Gnomad OTH

AF:

0.312

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000734

AC:

104

AN:

1416492

Hom.:

Cov.:

AF XY:

0.0000668

AC XY:

AN XY:

703460

show subpopulations

Gnomad4 AFR exome

AF:

0.000123

Gnomad4 AMR exome

AF:

0.0000231

Gnomad4 ASJ exome

AF:

0.000202

Gnomad4 EAS exome

AF:

0.0000828

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.000684

Gnomad4 NFE exome

AF:

0.0000377

Gnomad4 OTH exome

AF:

0.000104

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff

AF:

0.362

AC:

27431

AN:

75794

Hom.:

Cov.:

AF XY:

0.364

AC XY:

13880

AN XY:

38160

show subpopulations

Gnomad4 AFR

AF:

0.355

Gnomad4 AMR

AF:

0.349

Gnomad4 ASJ

AF:

0.395

Gnomad4 EAS

AF:

0.276

Gnomad4 SAS

AF:

0.303

Gnomad4 FIN

AF:

0.336

Gnomad4 NFE

AF:

0.385

Gnomad4 OTH

AF:

0.314

Alfa

AF:

0.108

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital

Jan 02, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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