rs2571236

chr18-57789442-G-A

Variant summary

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

The NM_001374385.1(ATP8B1):c.-26+13556C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 152,008 control chromosomes in the GnomAD database, including 5,754 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 0.25 (5754 hom., cov: 32)
• Consequence: ATP8B1 NM_001374385.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.112

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP8B1	NM_001374385.1	c.-26+13556C>T		intron_variant		ENST00000648908.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP8B1	ENST00000648908.2	c.-26+13556C>T		intron_variant			NM_001374385.1	P1
ATP8B1	ENST00000591728.1	c.-23+13556C>T		intron_variant, NMD_transcript_variant		3
ATP8B1	ENST00000642462.1	c.-26+12490C>T		intron_variant, NMD_transcript_variant
ATP8B1	ENST00000648039.1	c.-26+13556C>T		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38401 AN: 151890 Hom.: 5746 Cov.: 32

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.00810

Gnomad SAS AF: 0.0661

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.253 AC: 38444 AN: 152008 Hom.: 5754 Cov.: 32 AF XY: 0.245 AC XY: 18175 AN XY: 74288

Gnomad4 AFR AF: 0.408

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.00812

Gnomad4 SAS AF: 0.0659

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.247

Alfa AF: 0.258 Hom.: 1452

Bravo AF: 0.262

Asia WGS AF: 0.0750 AC: 262 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.4
Dann	Benign	0.40

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: rs2571236; hg19: chr18-55456674;