18-57646548-T-C

Position:

chr18-57646548-T-C

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_001374385.1(ATP8B1):c.*1940A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0049 in 152,778 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0049 ( 9 hom., cov: 33)

Exomes 𝑓: 0.0047 ( 0 hom. )

Consequence

ATP8B1
NM_001374385.1 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.687

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:

(HGNC:):

links:

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

ATP8B1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.28).

BP6

Variant 18-57646548-T-C is Benign according to our data. Variant chr18-57646548-T-C is described in ClinVar as [Benign]. Clinvar id is 327439.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0049 (746/152350) while in subpopulation EAS AF= 0.0439 (228/5190). AF 95% confidence interval is 0.0393. There are 9 homozygotes in gnomad4. There are 410 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP8B1	NM_001374385.1 linkuse as main transcript	c.*1940A>G		3_prime_UTR_variant	28/28	ENST00000648908.2	NP_001361314.1
ATP8B1-AS1	NR_164148.1 linkuse as main transcript	n.682+4496T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
ATP8B1	ENST00000648908.2 linkuse as main transcript	c.*1940A>G	3_prime_UTR_variant	28/28		NM_001374385.1	ENSP00000497896	P1
	ENST00000588925.5 linkuse as main transcript	n.570+4496T>C	intron_variant, non_coding_transcript_variant		2
ATP8B1-AS1	ENST00000592201.1 linkuse as main transcript	n.663+4496T>C	intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.00489

AC:

745

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000627

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0205

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.0442

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00184

Gnomad OTH

AF:

0.0105

GnomAD4 exome

AF:

0.00467

AC:

AN:

428

Hom.:

Cov.:

AF XY:

0.00781

AC XY:

AN XY:

256

show subpopulations

Gnomad4 FIN exome

AF:

0.00474

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00490

AC:

746

AN:

152350

Hom.:

Cov.:

AF XY:

0.00550

AC XY:

410

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.000625

Gnomad4 AMR

AF:

0.0208

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.0439

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.00151

Gnomad4 NFE

AF:

0.00184

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00391

Hom.:

Bravo

AF:

0.00681

Asia WGS

AF:

0.0120

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

-0.28

CADD

Benign

DANN

Benign

0.85

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