12-52951046-C-T

Position:

• chr12-52951046-C-T

Variant summary

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

The ENST00000388835.4(KRT18):​c.657+140C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 761,054 control chromosomes in the GnomAD database, including 57,581 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 0.38 (11592 hom., cov: 32)
  • Exomes 𝑓: 0.38 (45989 hom.)
• Consequence: KRT18 ENST00000388835.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74

Genes affected

KRT18 (HGNC:6430): (keratin 18) KRT18 encodes the type I intermediate filament chain keratin 18. Keratin 18, together with its filament partner keratin 8, are perhaps the most commonly found members of the intermediate filament gene family. They are expressed in single layer epithelial tissues of the body. Mutations in this gene have been linked to cryptogenic cirrhosis. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT18	NM_000224.3	c.657+140C>T		intron_variant		ENST00000388835.4	NP_000215.1
KRT18	NM_199187.2	c.657+140C>T		intron_variant			NP_954657.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT18	ENST00000388835.4	c.657+140C>T		intron_variant		1	NM_000224.3	ENSP00000373487	P1

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58402 AN: 151908 Hom.: 11586 Cov.: 32

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.401

GnomAD4 exome AF: 0.379 AC: 230707 AN: 609028 Hom.: 45989 AF XY: 0.380 AC XY: 119918 AN XY: 315900

Gnomad4 AFR exome AF: 0.370

Gnomad4 AMR exome AF: 0.522

Gnomad4 ASJ exome AF: 0.421

Gnomad4 EAS exome AF: 0.558

Gnomad4 SAS exome AF: 0.399

Gnomad4 FIN exome AF: 0.292

Gnomad4 NFE exome AF: 0.359

Gnomad4 OTH exome AF: 0.386

GnomAD4 genome AF: 0.384 AC: 58439 AN: 152026 Hom.: 11592 Cov.: 32 AF XY: 0.385 AC XY: 28640 AN XY: 74314

Gnomad4 AFR AF: 0.379

Gnomad4 AMR AF: 0.466

Gnomad4 ASJ AF: 0.416

Gnomad4 EAS AF: 0.583

Gnomad4 SAS AF: 0.420

Gnomad4 FIN AF: 0.271

Gnomad4 NFE AF: 0.367

Gnomad4 OTH AF: 0.406

Alfa AF: 0.379 Hom.: 23225

Bravo AF: 0.404

Asia WGS AF: 0.477 AC: 1660 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.5
DANN	Benign	0.70

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: rs2070876; hg19: chr12-53344830;