rs4941043

chr18-57756707-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001374385.1(ATP8B1):c.-25-24875G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 151,404 control chromosomes in the GnomAD database, including 25,062 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.57 (25062 hom., cov: 30)
• Consequence: ATP8B1 NM_001374385.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.435

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP8B1	NM_001374385.1	c.-25-24875G>T		intron_variant		ENST00000648908.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP8B1	ENST00000648908.2	c.-25-24875G>T		intron_variant			NM_001374385.1	P1
ATP8B1	ENST00000591728.1	c.-22-24878G>T		intron_variant, NMD_transcript_variant		3
ATP8B1	ENST00000642462.1	c.-25-24875G>T		intron_variant, NMD_transcript_variant
ATP8B1	ENST00000648039.1	c.-25-24875G>T		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86432 AN: 151286 Hom.: 25045 Cov.: 30

Gnomad AFR AF: 0.531

Gnomad AMI AF: 0.854

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.672

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.599

Gnomad OTH AF: 0.555

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.571 AC: 86481 AN: 151404 Hom.: 25062 Cov.: 30 AF XY: 0.570 AC XY: 42152 AN XY: 73932

Gnomad4 AFR AF: 0.531

Gnomad4 AMR AF: 0.544

Gnomad4 ASJ AF: 0.672

Gnomad4 EAS AF: 0.391

Gnomad4 SAS AF: 0.696

Gnomad4 FIN AF: 0.569

Gnomad4 NFE AF: 0.599

Gnomad4 OTH AF: 0.558

Alfa AF: 0.593 Hom.: 33436

Bravo AF: 0.560

Asia WGS AF: 0.547 AC: 1903 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.2
Dann	Benign	0.62

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

Other links and lift over

dbSNP: rs4941043; hg19: chr18-55423939;