12-52903536-G-A

Position:

• chr12-52903536-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_002273.4(KRT8):​c.324+1122C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 152,102 control chromosomes in the GnomAD database, including 10,515 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 0.37 (10514 hom., cov: 32)
  • Exomes 𝑓: 0.39 (1 hom.)
• Consequence: KRT8 NM_002273.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.17

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRT8	NM_002273.4	c.324+1122C>T		intron_variant		ENST00000692008.1
KRT8	NM_001256282.2	c.408+1122C>T		intron_variant
KRT8	NM_001256293.2	c.324+1122C>T		intron_variant
KRT8	NR_045962.2	n.775+1122C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRT8	ENST00000692008.1	c.324+1122C>T		intron_variant			NM_002273.4	P2

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55567 AN: 151956 Hom.: 10489 Cov.: 32

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.356

GnomAD4 exome AF: 0.393 AC: 11 AN: 28 Hom.: 1 Cov.: 0 AF XY: 0.444 AC XY: 8 AN XY: 18

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.400

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.366 AC: 55637 AN: 152074 Hom.: 10514 Cov.: 32 AF XY: 0.358 AC XY: 26583 AN XY: 74342

Gnomad4 AFR AF: 0.382

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.324

Gnomad4 EAS AF: 0.137

Gnomad4 SAS AF: 0.322

Gnomad4 FIN AF: 0.276

Gnomad4 NFE AF: 0.406

Gnomad4 OTH AF: 0.357

Alfa AF: 0.395 Hom.: 17456

Bravo AF: 0.369

Asia WGS AF: 0.231 AC: 802 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	18
DANN	Benign	0.93

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: rs7964223; hg19: chr12-53297320; COSMIC: COSV53178584; COSMIC: COSV53178584;