rs4919743

Variant names:

• chr12-52915800-G-A
• rs4919743
• ENST00000552150.5:c.38+10612C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000552150.5(KRT8):​c.38+10612C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,126 control chromosomes in the GnomAD database, including 1,222 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.12 (1222 hom., cov: 32)
• Consequence: KRT8 ENST00000552150.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.53
• Publications: 13 publications found

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

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT8	NM_001256282.2	c.38+10612C>T		intron_variant	Intron 1 of 8		NP_001243211.1
KRT8	NM_001256293.2	c.-46-10773C>T		intron_variant	Intron 1 of 8		NP_001243222.1
KRT8	NR_045962.2	n.406-10773C>T		intron_variant	Intron 1 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT8	ENST00000552150.5	c.38+10612C>T		intron_variant	Intron 1 of 8	1		ENSP00000449404.1
KRT8	ENST00000546897.5	c.-46-10773C>T		intron_variant	Intron 1 of 8	2		ENSP00000447402.1
KRT8	ENST00000552551.5	c.-46-10773C>T		intron_variant	Intron 1 of 8	2		ENSP00000447566.1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18558 AN: 152008 Hom.: 1220 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.0877

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0406

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.113

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.122 AC: 18567 AN: 152126 Hom.: 1222 Cov.: 32 AF XY: 0.120 AC XY: 8933 AN XY: 74362

African (AFR) AF: 0.154 AC: 6386 AN: 41484

American (AMR) AF: 0.0877 AC: 1339 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 565 AN: 3468

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5188

South Asian (SAS) AF: 0.0406 AC: 196 AN: 4826

European-Finnish (FIN) AF: 0.151 AC: 1598 AN: 10568

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.119 AC: 8077 AN: 68004

Other (OTH) AF: 0.112 AC: 236 AN: 2112

Alfa AF: 0.123 Hom.: 677

Bravo AF: 0.118

Asia WGS AF: 0.0310 AC: 109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	16
DANN	Benign	0.72
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4919743; hg19: chr12-53309584;