18-57697620-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001374385.1(ATP8B1):c.696T>C(p.Asp232Asp) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.999 in 1,613,916 control chromosomes in the GnomAD database, including 805,295 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 Benign (★★).

Frequency

Genomes: 𝑓 0.99 ( 75238 hom., cov: 29)

Exomes 𝑓: 1.0 ( 730057 hom. )

Consequence

ATP8B1
NM_001374385.1 splice_region, synonymous

Scores

Splicing: ADA: 0.00002227

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.0390

Publications

25 publications found

Variant links:

Genes affected

ATP8B1 (HGNC:3706): (ATPase phospholipid transporting 8B1) This gene encodes a member of the P-type cation transport ATPase family, which belongs to the subfamily of aminophospholipid-transporting ATPases. The aminophospholipid translocases transport phosphatidylserine and phosphatidylethanolamine from one side of a bilayer to another. Mutations in this gene may result in progressive familial intrahepatic cholestasis type 1 and in benign recurrent intrahepatic cholestasis. [provided by RefSeq, Jul 2008]

ATP8B1 links:

ATP8B1-AS1 (HGNC:56042): (ATP8B1 antisense RNA 1)

ATP8B1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 18-57697620-A-G is Benign according to our data. Variant chr18-57697620-A-G is described in ClinVar as [Benign]. Clinvar id is 259826.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.039 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP8B1	NM_001374385.1 link	c.696T>C	p.Asp232Asp	splice_region_variant, synonymous_variant	Exon 8 of 28	ENST00000648908.2	NP_001361314.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP8B1	ENST00000648908.2 link	c.696T>C	p.Asp232Asp	splice_region_variant, synonymous_variant	Exon 8 of 28		NM_001374385.1	ENSP00000497896.1		O43520

Frequencies

GnomAD3 genomes

AF:

0.994

AC:

151182

AN:

152032

Hom.:

75182

Cov.:

show subpopulations

Gnomad AFR

AF:

0.981

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.998

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.996

GnomAD2 exomes

AF:

0.998

AC:

250904

AN:

251298

AF XY:

0.999

show subpopulations

Gnomad AFR exome

AF:

0.980

Gnomad AMR exome

AF:

0.999

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

0.999

GnomAD4 exome

AF:

0.999

AC:

1460930

AN:

1461766

Hom.:

730057

Cov.:

AF XY:

0.999

AC XY:

726823

AN XY:

727192

show subpopulations

African (AFR)

AF:

0.981

AC:

32836

AN:

33478

American (AMR)

AF:

0.999

AC:

44677

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

26131

AN:

26136

East Asian (EAS)

AF:

1.00

AC:

39689

AN:

39700

South Asian (SAS)

AF:

1.00

AC:

86252

AN:

86256

European-Finnish (FIN)

AF:

1.00

AC:

53395

AN:

53400

Middle Eastern (MID)

AF:

1.00

AC:

5767

AN:

5768

European-Non Finnish (NFE)

AF:

1.00

AC:

1111862

AN:

1111912

Other (OTH)

AF:

0.999

AC:

60321

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

145

193

241

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.994

AC:

151297

AN:

152150

Hom.:

75238

Cov.:

AF XY:

0.995

AC XY:

73997

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.981

AC:

40691

AN:

41490

American (AMR)

AF:

0.998

AC:

15252

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

3471

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5156

AN:

5158

South Asian (SAS)

AF:

1.00

AC:

4791

AN:

4792

European-Finnish (FIN)

AF:

1.00

AC:

10618

AN:

10618

Middle Eastern (MID)

AF:

1.00

AC:

294

AN:

294

European-Non Finnish (NFE)

AF:

1.00

AC:

68006

AN:

68012

Other (OTH)

AF:

0.996

AC:

2106

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

127

169

211

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.998

Hom.:

103586

Bravo

AF:

0.994

Asia WGS

AF:

0.999

AC:

3475

AN:

3478

EpiCase

AF:

1.00

EpiControl

AF:

1.00

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Dec 02, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Feb 28, 2025

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Progressive familial intrahepatic cholestasis type 1

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cholestasis, intrahepatic, of pregnancy, 1

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

0.78

(source)

DANN

Benign

0.80

PhyloP100

-0.039

Mutation Taster

=81/19

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000022

dbscSNV1_RF

Benign

0.0020

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

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18-57697620-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over