dbSNP rs2070875: KRT18:c.500+124G>T (chr12-52950534-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000224.3(KRT18):c.500+124G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0911 in 839,932 control chromosomes in the GnomAD database, including 12,826 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 0.085 ( 1658 hom., cov: 32)

Exomes 𝑓: 0.092 ( 11168 hom. )

Consequence

KRT18
NM_000224.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.894

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

cirrhosis, familial
Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

KRT18 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT18	NM_000224.3 link	c.500+124G>T		intron_variant	Intron 2 of 6	ENST00000388835.4	NP_000215.1	P05783A0A024RAY2
KRT18	NM_199187.2 link	c.500+124G>T		intron_variant	Intron 3 of 7		NP_954657.1	P05783A0A024RAY2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT18	ENST00000388835.4 link	c.500+124G>T		intron_variant	Intron 2 of 6	1	NM_000224.3	ENSP00000373487.3		P05783

Frequencies

GnomAD3 genomes

AF:

0.0849

AC:

12911

AN:

151998

Hom.:

1648

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0941

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.226

Gnomad ASJ

AF:

0.0323

Gnomad EAS

AF:

0.551

Gnomad SAS

AF:

0.243

Gnomad FIN

AF:

0.0353

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0129

Gnomad OTH

AF:

0.0900

GnomAD4 exome

AF:

0.0925

AC:

63590

AN:

687816

Hom.:

11168

Cov.:

AF XY:

0.0927

AC XY:

34217

AN XY:

369252

show subpopulations

African (AFR)

AF:

0.0972

AC:

1826

AN:

18780

American (AMR)

AF:

0.392

AC:

16839

AN:

43008

Ashkenazi Jewish (ASJ)

AF:

0.0297

AC:

613

AN:

20634

East Asian (EAS)

AF:

0.538

AC:

19505

AN:

36232

South Asian (SAS)

AF:

0.210

AC:

14529

AN:

69270

European-Finnish (FIN)

AF:

0.0336

AC:

1639

AN:

48782

Middle Eastern (MID)

AF:

0.0441

AC:

186

AN:

4216

European-Non Finnish (NFE)

AF:

0.0138

AC:

5666

AN:

411856

Other (OTH)

AF:

0.0795

AC:

2787

AN:

35038

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

2321

4641

6962

9282

11603

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

568

1136

1704

2272

2840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0850

AC:

12937

AN:

152116

Hom.:

1658

Cov.:

AF XY:

0.0938

AC XY:

6975

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.0940

AC:

3901

AN:

41504

American (AMR)

AF:

0.227

AC:

3461

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.0323

AC:

112

AN:

3470

East Asian (EAS)

AF:

0.550

AC:

2830

AN:

5142

South Asian (SAS)

AF:

0.242

AC:

1163

AN:

4810

European-Finnish (FIN)

AF:

0.0353

AC:

375

AN:

10610

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0129

AC:

880

AN:

67996

Other (OTH)

AF:

0.0975

AC:

206

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

476

951

1427

1902

2378

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

142

284

426

568

710

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0745

Hom.:

533

Bravo

AF:

0.104

Asia WGS

AF:

0.341

AC:

1185

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.6

(source)

DANN

Benign

0.48

PhyloP100

-0.89

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over