Variant rs319439 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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:

ENSG00000267787 (HGNC:):

ENSG00000267787 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 259827.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-57697598-G-A is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
ATP8B1	NM_001374385.1 linkuse as main transcript	c.698+20C>T		intron_variant		ENST00000648908.2	NP_001361314.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP8B1	ENST00000648908.2 linkuse as main transcript	c.698+20C>T		intron_variant			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

GnomAD3 exomes

AF:

0.487

AC:

122250

AN:

250774

Hom.:

31394

AF XY:

0.480

AC XY:

65060

AN XY:

135652

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 SAS exome

AF:

0.382

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

Gnomad4 AFR exome

AF:

0.253

Gnomad4 AMR exome

AF:

0.638

Gnomad4 ASJ exome

AF:

0.529

Gnomad4 EAS exome

AF:

0.711

Gnomad4 SAS exome

AF:

0.380

Gnomad4 FIN exome

AF:

0.446

Gnomad4 NFE exome

AF:

0.477

Gnomad4 OTH exome

AF:

0.478

GnomAD4 genome

AF:

0.430

AC:

65360

AN:

151900

Hom.:

15074

Cov.:

AF XY:

0.430

AC XY:

31892

AN XY:

74236

show subpopulations

Gnomad4 AFR

AF:

0.269

Gnomad4 AMR

AF:

0.552

Gnomad4 ASJ

AF:

0.520

Gnomad4 EAS

AF:

0.684

Gnomad4 SAS

AF:

0.380

Gnomad4 FIN

AF:

0.449

Gnomad4 NFE

AF:

0.479

Gnomad4 OTH

AF:

0.456

Alfa

AF:

0.477

Hom.:

30603

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 02, 2015	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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Cholestasis, intrahepatic, of pregnancy, 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Progressive familial intrahepatic cholestasis type 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.5

DANN

Benign

0.47

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

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