chr12-52923037-G-A

Variant names:

• chr12-52923037-G-A
• rs73110471
• ENST00000552150.5:c.38+3375C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000552150.5(KRT8):​c.38+3375C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 152,166 control chromosomes in the GnomAD database, including 848 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 0.10 (848 hom., cov: 32)
• Consequence: KRT8 ENST00000552150.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.150
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000552150.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT8	NM_001256282.2		c.38+3375C>T		intron	N/A	NP_001243211.1
	KRT8	NM_001256293.2		c.-46-18010C>T		intron	N/A	NP_001243222.1
	KRT8	NR_045962.2		n.406-18010C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT8	ENST00000552150.5	TSL:1	c.38+3375C>T		intron	N/A	ENSP00000449404.1
	KRT8	ENST00000546897.5	TSL:2	c.-46-18010C>T		intron	N/A	ENSP00000447402.1
	KRT8	ENST00000552551.5	TSL:2	c.-46-18010C>T		intron	N/A	ENSP00000447566.1

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15268 AN: 152048 Hom.: 849 Cov.: 32

Gnomad AFR AF: 0.0788

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.0772

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.0400

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.0977

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

GnomAD4 genome AF: 0.100 AC: 15272 AN: 152166 Hom.: 848 Cov.: 32 AF XY: 0.0993 AC XY: 7385 AN XY: 74384

African (AFR) AF: 0.0787 AC: 3269 AN: 41524

American (AMR) AF: 0.0771 AC: 1179 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 566 AN: 3468

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5178

South Asian (SAS) AF: 0.0403 AC: 194 AN: 4818

European-Finnish (FIN) AF: 0.151 AC: 1602 AN: 10580

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.119 AC: 8090 AN: 68002

Other (OTH) AF: 0.0967 AC: 204 AN: 2110

Alfa AF: 0.0804 Hom.: 134

Bravo AF: 0.0935

Asia WGS AF: 0.0280 AC: 99 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.1
DANN	Benign	0.63
PhyloP100		-0.15
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: rs73110471; hg19: chr12-53316821;