chr18-57650359-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001374385.1(ATP8B1):c.3531+8G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 1,611,714 control chromosomes in the GnomAD database, including 20,984 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1453 hom., cov: 32)

Exomes 𝑓: 0.16 ( 19531 hom. )

Consequence

ATP8B1
NM_001374385.1 splice_region, intron

Scores

Splicing: ADA: 0.0001719

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.578

Publications

10 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 18-57650359-C-A is Benign according to our data. Variant chr18-57650359-C-A is described in ClinVar as [Benign]. Clinvar id is 259822.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP8B1	NM_001374385.1 link	c.3531+8G>T		splice_region_variant, intron_variant	Intron 27 of 27	ENST00000648908.2	NP_001361314.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP8B1	ENST00000648908.2 link	c.3531+8G>T		splice_region_variant, intron_variant	Intron 27 of 27		NM_001374385.1	ENSP00000497896.1		O43520

Frequencies

GnomAD3 genomes

AF:

0.122

AC:

18489

AN:

152064

Hom.:

1453

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0314

Gnomad AMI

AF:

0.0570

Gnomad AMR

AF:

0.154

Gnomad ASJ

AF:

0.193

Gnomad EAS

AF:

0.00845

Gnomad SAS

AF:

0.126

Gnomad FIN

AF:

0.144

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.171

Gnomad OTH

AF:

0.139

GnomAD2 exomes

AF:

0.140

AC:

35128

AN:

251462

AF XY:

0.144

show subpopulations

Gnomad AFR exome

AF:

0.0295

Gnomad AMR exome

AF:

0.141

Gnomad ASJ exome

AF:

0.203

Gnomad EAS exome

AF:

0.00549

Gnomad FIN exome

AF:

0.135

Gnomad NFE exome

AF:

0.172

Gnomad OTH exome

AF:

0.152

GnomAD4 exome

AF:

0.159

AC:

232074

AN:

1459532

Hom.:

19531

Cov.:

AF XY:

0.158

AC XY:

115035

AN XY:

726112

show subpopulations

African (AFR)

AF:

0.0256

AC:

855

AN:

33416

American (AMR)

AF:

0.144

AC:

6442

AN:

44648

Ashkenazi Jewish (ASJ)

AF:

0.197

AC:

5142

AN:

26078

East Asian (EAS)

AF:

0.00546

AC:

216

AN:

39578

South Asian (SAS)

AF:

0.136

AC:

11702

AN:

86188

European-Finnish (FIN)

AF:

0.139

AC:

7382

AN:

53150

Middle Eastern (MID)

AF:

0.139

AC:

800

AN:

5752

European-Non Finnish (NFE)

AF:

0.172

AC:

190854

AN:

1110490

Other (OTH)

AF:

0.144

AC:

8681

AN:

60232

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

10236

20472

30707

40943

51179

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.121

AC:

18484

AN:

152182

Hom.:

1453

Cov.:

AF XY:

0.120

AC XY:

8891

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.0313

AC:

1301

AN:

41530

American (AMR)

AF:

0.154

AC:

2344

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.193

AC:

668

AN:

3470

East Asian (EAS)

AF:

0.00847

AC:

AN:

5194

South Asian (SAS)

AF:

0.127

AC:

610

AN:

4822

European-Finnish (FIN)

AF:

0.144

AC:

1522

AN:

10582

Middle Eastern (MID)

AF:

0.139

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.171

AC:

11615

AN:

68002

Other (OTH)

AF:

0.136

AC:

287

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

800

1601

2401

3202

4002

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.154

Hom.:

1232

Bravo

AF:

0.117

Asia WGS

AF:

0.0700

AC:

245

AN:

3478

EpiCase

AF:

0.166

EpiControl

AF:

0.169

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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

- -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

-0.80

CADD

Benign

7.4

(source)

DANN

Benign

0.37

PhyloP100

0.58

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00017

dbscSNV1_RF

Benign

0.016

SpliceAI score (max)

0.26

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.26

Position offset: -34

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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chr18-57650359-C-A

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