rs4941043

Variant names:

• chr18-57756707-C-A
• rs4941043
• NM_001374385.1:c.-25-24875G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• progressive familial intrahepatic cholestasis type 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Laboratory for Molecular Medicine, Orphanet, Labcorp Genetics (formerly Invitae)
• cholestasis, intrahepatic, of pregnancy, 1

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ATP8B1	NM_001374385.1	c.-25-24875G>T		intron_variant	Intron 1 of 27	ENST00000648908.2	NP_001361314.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP8B1	ENST00000648908.2	c.-25-24875G>T		intron_variant	Intron 1 of 27		NM_001374385.1	ENSP00000497896.1
ATP8B1	ENST00000591728.1	n.-22-24878G>T		intron_variant	Intron 1 of 4	3		ENSP00000467767.1
ATP8B1	ENST00000642462.1	n.-25-24875G>T		intron_variant	Intron 1 of 28			ENSP00000494712.1
ATP8B1	ENST00000648039.1	n.-25-24875G>T		intron_variant	Intron 1 of 28			ENSP00000497863.1

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

African (AFR) AF: 0.531 AC: 21868 AN: 41220

American (AMR) AF: 0.544 AC: 8287 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.672 AC: 2328 AN: 3466

East Asian (EAS) AF: 0.391 AC: 2008 AN: 5140

South Asian (SAS) AF: 0.696 AC: 3339 AN: 4794

European-Finnish (FIN) AF: 0.569 AC: 5945 AN: 10440

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.599 AC: 40610 AN: 67836

Other (OTH) AF: 0.558 AC: 1171 AN: 2098

Alfa AF: 0.585 Hom.: 56795

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
PhyloP100		0.43
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4941043; hg19: chr18-55423939;