rs34255016

Positions:

chr18-57648477-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001374385.1(ATP8B1):c.*11C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0142 in 1,610,924 control chromosomes in the GnomAD database, including 216 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0097 ( 23 hom., cov: 32)

Exomes 𝑓: 0.015 ( 193 hom. )

Consequence

ATP8B1
NM_001374385.1 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.67

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:

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=-0.86).

BP6

Variant 18-57648477-G-A is Benign according to our data. Variant chr18-57648477-G-A is described in ClinVar as [Benign]. Clinvar id is 259814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-57648477-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0097 (1477/152346) while in subpopulation NFE AF= 0.015 (1018/68032). AF 95% confidence interval is 0.0142. There are 23 homozygotes in gnomad4. There are 677 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 23 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP8B1	NM_001374385.1 link	c.*11C>T		3_prime_UTR_variant	28/28	ENST00000648908.2	NP_001361314.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP8B1	ENST00000648908 link	c.*11C>T		3_prime_UTR_variant	28/28		NM_001374385.1	ENSP00000497896.1		O43520

Frequencies

GnomAD3 genomes

AF:

0.00971

AC:

1478

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00258

Gnomad AMI

AF:

0.0581

Gnomad AMR

AF:

0.00988

Gnomad ASJ

AF:

0.0187

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00559

Gnomad FIN

AF:

0.00245

Gnomad MID

AF:

0.0159

Gnomad NFE

AF:

0.0150

Gnomad OTH

AF:

0.0124

GnomAD3 exomes

AF:

0.00943

AC:

2291

AN:

243008

Hom.:

AF XY:

0.00943

AC XY:

1250

AN XY:

132584

show subpopulations

Gnomad AFR exome

AF:

0.00256

Gnomad AMR exome

AF:

0.00726

Gnomad ASJ exome

AF:

0.0192

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00357

Gnomad FIN exome

AF:

0.00259

Gnomad NFE exome

AF:

0.0147

Gnomad OTH exome

AF:

0.0126

GnomAD4 exome

AF:

0.0146

AC:

21348

AN:

1458578

Hom.:

193

Cov.:

AF XY:

0.0145

AC XY:

10506

AN XY:

725604

show subpopulations

Gnomad4 AFR exome

AF:

0.00269

Gnomad4 AMR exome

AF:

0.00771

Gnomad4 ASJ exome

AF:

0.0216

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00385

Gnomad4 FIN exome

AF:

0.00308

Gnomad4 NFE exome

AF:

0.0171

Gnomad4 OTH exome

AF:

0.0131

GnomAD4 genome

AF:

0.00970

AC:

1477

AN:

152346

Hom.:

Cov.:

AF XY:

0.00909

AC XY:

677

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00257

Gnomad4 AMR

AF:

0.00987

Gnomad4 ASJ

AF:

0.0187

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00559

Gnomad4 FIN

AF:

0.00245

Gnomad4 NFE

AF:

0.0150

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.0136

Hom.:

Bravo

AF:

0.0108

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 13, 2016	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:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Progressive familial intrahepatic cholestasis type 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.19

DANN

Benign

0.72

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