12-52898449-TG-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_002273.4(KRT8):c.1261+11del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.031 in 1,612,462 control chromosomes in the GnomAD database, including 1,009 homozygotes. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.024 (73 hom., cov: 32)
  • Exomes 𝑓: 0.032 (936 hom.)
• Consequence: KRT8 NM_002273.4 intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.826

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRT8	NM_002273.4	c.1261+11del		intron_variant		ENST00000692008.1
KRT8	NM_001256282.2	c.1345+11del		intron_variant
KRT8	NM_001256293.2	c.1261+11del		intron_variant
KRT8	NR_045962.2	n.1712+11del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRT8	ENST00000692008.1	c.1261+11del		intron_variant			NM_002273.4	P2

Frequencies

GnomAD3 genomes AF: 0.0235 AC: 3572 AN: 152100 Hom.: 67 Cov.: 32

Gnomad AFR AF: 0.00845

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0515

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.0137

Gnomad SAS AF: 0.0401

Gnomad FIN AF: 0.0160

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0284

Gnomad OTH AF: 0.0201

GnomAD3 exomes AF: 0.0349 AC: 8659 AN: 247864 Hom.: 263 AF XY: 0.0336 AC XY: 4509 AN XY: 134316

Gnomad AFR exome AF: 0.00704

Gnomad AMR exome AF: 0.0972

Gnomad ASJ exome AF: 0.00311

Gnomad EAS exome AF: 0.00897

Gnomad SAS exome AF: 0.0495

Gnomad FIN exome AF: 0.0173

Gnomad NFE exome AF: 0.0266

Gnomad OTH exome AF: 0.0308

GnomAD4 exome AF: 0.0317 AC: 46313 AN: 1460244 Hom.: 936 Cov.: 32 AF XY: 0.0317 AC XY: 23009 AN XY: 726342

Gnomad4 AFR exome AF: 0.00532

Gnomad4 AMR exome AF: 0.0906

Gnomad4 ASJ exome AF: 0.00295

Gnomad4 EAS exome AF: 0.0300

Gnomad4 SAS exome AF: 0.0475

Gnomad4 FIN exome AF: 0.0182

Gnomad4 NFE exome AF: 0.0305

Gnomad4 OTH exome AF: 0.0282

GnomAD4 genome AF: 0.0236 AC: 3596 AN: 152218 Hom.: 73 Cov.: 32 AF XY: 0.0233 AC XY: 1732 AN XY: 74422

Gnomad4 AFR AF: 0.00840

Gnomad4 AMR AF: 0.0524

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.0138

Gnomad4 SAS AF: 0.0402

Gnomad4 FIN AF: 0.0160

Gnomad4 NFE AF: 0.0284

Gnomad4 OTH AF: 0.0236

Alfa AF: 0.0236 Hom.: 10

Bravo AF: 0.0259

Asia WGS AF: 0.0350 AC: 122 AN: 3476

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not provided Other:1

not provided, no classification provided

literature only

Epithelial Biology; Institute of Medical Biology, Singapore

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Computational scores

Source: dbNSFP v4.3

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: rs267607664; hg19: chr12-53292233;