12-52898633-T-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_002273.4(KRT8):c.1202+46A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00423 in 1,612,810 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.0042 (4 hom., cov: 33)
  • Exomes 𝑓: 0.0042 (24 hom.)
• Consequence: KRT8 NM_002273.4 intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -0.748

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.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS2: High Homozygotes in GnomAd at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRT8	NM_002273.4	c.1202+46A>T		intron_variant		ENST00000692008.1
KRT8	NM_001256282.2	c.1286+46A>T		intron_variant
KRT8	NM_001256293.2	c.1202+46A>T		intron_variant
KRT8	NR_045962.2	n.1653+46A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRT8	ENST00000692008.1	c.1202+46A>T		intron_variant			NM_002273.4	P2

Frequencies

GnomAD3 genomes AF: 0.00425 AC: 646 AN: 152120 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00308

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0230

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00468

Gnomad OTH AF: 0.00574

GnomAD3 exomes AF: 0.00476 AC: 1197 AN: 251340 Hom.: 14 AF XY: 0.00473 AC XY: 642 AN XY: 135854

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.00211

Gnomad ASJ exome AF: 0.00109

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000980

Gnomad FIN exome AF: 0.0246

Gnomad NFE exome AF: 0.00450

Gnomad OTH exome AF: 0.00554

GnomAD4 exome AF: 0.00423 AC: 6178 AN: 1460572 Hom.: 24 Cov.: 32 AF XY: 0.00420 AC XY: 3052 AN XY: 726694

Gnomad4 AFR exome AF: 0.000688

Gnomad4 AMR exome AF: 0.00197

Gnomad4 ASJ exome AF: 0.00119

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000974

Gnomad4 FIN exome AF: 0.0238

Gnomad4 NFE exome AF: 0.00401

Gnomad4 OTH exome AF: 0.00360

GnomAD4 genome AF: 0.00424 AC: 646 AN: 152238 Hom.: 4 Cov.: 33 AF XY: 0.00505 AC XY: 376 AN XY: 74442

Gnomad4 AFR AF: 0.000481

Gnomad4 AMR AF: 0.00307

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.0230

Gnomad4 NFE AF: 0.00468

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.00441 Hom.: 0

Bravo AF: 0.00277

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.16
Dann	Benign	0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs189690662; hg19: chr12-53292417;