Variant 12-52950324-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000388835.4(KRT18):c.418-4C>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0011 in 1,608,378 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.00081 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 5 hom. )

Consequence

KRT18
ENST00000388835.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0001402

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: -0.196

Variant links:

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]

KRT18 links:

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ACMG classification

Classification made for transcript

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 123 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT18	NM_000224.3 linkuse as main transcript	c.418-4C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000388835.4	NP_000215.1
KRT18	NM_199187.2 linkuse as main transcript	c.418-4C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_954657.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT18	ENST00000388835.4 linkuse as main transcript	c.418-4C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_000224.3	ENSP00000373487	P1

Frequencies

GnomAD3 genomes

AF:

0.000815

AC:

124

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000917

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00118

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00119

AC:

299

AN:

251408

Hom.:

AF XY:

0.00126

AC XY:

171

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.00217

Gnomad ASJ exome

AF:

0.00258

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00154

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00116

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00114

AC:

1654

AN:

1456036

Hom.:

Cov.:

AF XY:

0.00119

AC XY:

859

AN XY:

724832

show subpopulations

Gnomad4 AFR exome

AF:

0.0000900

Gnomad4 AMR exome

AF:

0.00206

Gnomad4 ASJ exome

AF:

0.00318

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00214

Gnomad4 FIN exome

AF:

0.000112

Gnomad4 NFE exome

AF:

0.00106

Gnomad4 OTH exome

AF:

0.00164

GnomAD4 genome

AF:

0.000807

AC:

123

AN:

152342

Hom.:

Cov.:

AF XY:

0.000792

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.000192

Gnomad4 AMR

AF:

0.000915

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00118

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00148

Hom.:

Bravo

AF:

0.000914

EpiCase

AF:

0.00185

EpiControl

AF:

0.00237

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

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

2.9

DANN

Benign

0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00014

dbscSNV1_RF

Benign

0.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over