rs319439

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.698+20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 1,608,944 control chromosomes in the GnomAD database, including 184,694 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 15074 hom., cov: 31)

Exomes 𝑓: 0.48 ( 169620 hom. )

Consequence

ATP8B1
NM_001374385.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.221

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=-0.81).

BP6

Variant 18-57697598-G-A is Benign according to our data. Variant chr18-57697598-G-A is described in ClinVar as Benign. ClinVar VariationId is 259827.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP8B1	NM_001374385.1 link	c.698+20C>T		intron_variant	Intron 8 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.698+20C>T		intron_variant	Intron 8 of 27		NM_001374385.1	ENSP00000497896.1		O43520

Frequencies

GnomAD3 genomes

AF:

0.430

AC:

65310

AN:

151782

Hom.:

15055

Cov.:

show subpopulations

Gnomad AFR

AF:

0.269

Gnomad AMI

AF:

0.302

Gnomad AMR

AF:

0.552

Gnomad ASJ

AF:

0.520

Gnomad EAS

AF:

0.684

Gnomad SAS

AF:

0.380

Gnomad FIN

AF:

0.449

Gnomad MID

AF:

0.408

Gnomad NFE

AF:

0.479

Gnomad OTH

AF:

0.451

GnomAD2 exomes

AF:

0.487

AC:

122250

AN:

250774

AF XY:

0.480

show subpopulations

Gnomad AFR exome

AF:

0.260

Gnomad AMR exome

AF:

0.647

Gnomad ASJ exome

AF:

0.536

Gnomad EAS exome

AF:

0.677

Gnomad FIN exome

AF:

0.445

Gnomad NFE exome

AF:

0.472

Gnomad OTH exome

AF:

0.498

GnomAD4 exome

AF:

0.477

AC:

694706

AN:

1457044

Hom.:

169620

Cov.:

AF XY:

0.474

AC XY:

343967

AN XY:

725166

show subpopulations

African (AFR)

AF:

0.253

AC:

8438

AN:

33386

American (AMR)

AF:

0.638

AC:

28508

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.529

AC:

13817

AN:

26102

East Asian (EAS)

AF:

0.711

AC:

28217

AN:

39666

South Asian (SAS)

AF:

0.380

AC:

32782

AN:

86168

European-Finnish (FIN)

AF:

0.446

AC:

23764

AN:

53318

Middle Eastern (MID)

AF:

0.406

AC:

2336

AN:

5748

European-Non Finnish (NFE)

AF:

0.477

AC:

528068

AN:

1107688

Other (OTH)

AF:

0.478

AC:

28776

AN:

60254

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

16701

33403

50104

66806

83507

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15616

31232

46848

62464

78080

<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:

0.430

AC:

65360

AN:

151900

Hom.:

15074

Cov.:

AF XY:

0.430

AC XY:

31892

AN XY:

74236

show subpopulations

African (AFR)

AF:

0.269

AC:

11117

AN:

41390

American (AMR)

AF:

0.552

AC:

8423

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.520

AC:

1804

AN:

3468

East Asian (EAS)

AF:

0.684

AC:

3520

AN:

5148

South Asian (SAS)

AF:

0.380

AC:

1822

AN:

4796

European-Finnish (FIN)

AF:

0.449

AC:

4742

AN:

10564

Middle Eastern (MID)

AF:

0.408

AC:

120

AN:

294

European-Non Finnish (NFE)

AF:

0.479

AC:

32574

AN:

67972

Other (OTH)

AF:

0.456

AC:

963

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1786

3572

5357

7143

8929

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

600

1200

1800

2400

3000

<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:

0.468

Hom.:

67230

Bravo

AF:

0.438

Asia WGS

AF:

0.498

AC:

1729

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

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. -

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

- -

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

- -

Progressive familial intrahepatic cholestasis type 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

-0.81

CADD

Benign

2.5

(source)

DANN

Benign

0.47

PhyloP100

0.22

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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