rs73110471

Positions:

• chr12-52923037-G-A
• chr12-52923037-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001256282.2(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 NM_001256282.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.150

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT8	NM_001256282.2	c.38+3375C>T		intron_variant			NP_001243211.1
KRT8	NM_001256293.2	c.-46-18010C>T		intron_variant			NP_001243222.1
KRT8	NR_045962.2	n.406-18010C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT8	ENST00000552150.5	c.38+3375C>T		intron_variant		1		ENSP00000449404.1
KRT8	ENST00000546897.5	c.-46-18010C>T		intron_variant		2		ENSP00000447402.1
KRT8	ENST00000552551.5	c.-46-18010C>T		intron_variant		2		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

Gnomad4 AFR AF: 0.0787

Gnomad4 AMR AF: 0.0771

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0403

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.119

Gnomad4 OTH AF: 0.0967

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.1
DANN	Benign	0.63

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

Other links and lift over

dbSNP: rs73110471; hg19: chr12-53316821;