12-52950448-G-A

Position:

• chr12-52950448-G-A

Variant summary

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

The ENST00000388835.4(KRT18):​c.500+38G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00231 in 1,467,742 control chromosomes in the GnomAD database, including 12 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 0.0016 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (11 hom.)
• Consequence: KRT18 ENST00000388835.4 intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.785

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BS2: High AC in GnomAd4 at 247 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT18	NM_000224.3	c.500+38G>A		intron_variant		ENST00000388835.4	NP_000215.1
KRT18	NM_199187.2	c.500+38G>A		intron_variant			NP_954657.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT18	ENST00000388835.4	c.500+38G>A		intron_variant		1	NM_000224.3	ENSP00000373487	P1

Frequencies

GnomAD3 genomes AF: 0.00164 AC: 247 AN: 150562 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000465

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00142

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00467

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00222

Gnomad OTH AF: 0.00289

GnomAD3 exomes AF: 0.00179 AC: 446 AN: 249048 Hom.: 1 AF XY: 0.00200 AC XY: 270 AN XY: 135052

Gnomad AFR exome AF: 0.000446

Gnomad AMR exome AF: 0.00107

Gnomad ASJ exome AF: 0.000398

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000294

Gnomad FIN exome AF: 0.00461

Gnomad NFE exome AF: 0.00248

Gnomad OTH exome AF: 0.00214

GnomAD4 exome AF: 0.00239 AC: 3150 AN: 1317062 Hom.: 11 Cov.: 20 AF XY: 0.00234 AC XY: 1552 AN XY: 663278

Gnomad4 AFR exome AF: 0.000555

Gnomad4 AMR exome AF: 0.00130

Gnomad4 ASJ exome AF: 0.000514

Gnomad4 EAS exome AF: 0.0000256

Gnomad4 SAS exome AF: 0.000324

Gnomad4 FIN exome AF: 0.00345

Gnomad4 NFE exome AF: 0.00278

Gnomad4 OTH exome AF: 0.00221

GnomAD4 genome AF: 0.00164 AC: 247 AN: 150680 Hom.: 1 Cov.: 32 AF XY: 0.00185 AC XY: 136 AN XY: 73366

Gnomad4 AFR AF: 0.000464

Gnomad4 AMR AF: 0.00142

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00467

Gnomad4 NFE AF: 0.00222

Gnomad4 OTH AF: 0.00286

Alfa AF: 0.00143 Hom.: 0

Bravo AF: 0.00148

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.2
DANN	Benign	0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs143051595; hg19: chr12-53344232;