rs10503019

Variant names:

• chr18-57787145-G-A
• rs10503019
• NM_001374385.1:c.-26+15853C>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.-26+15853C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 152,076 control chromosomes in the GnomAD database, including 2,683 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 0.17 (2683 hom., cov: 32)
• Consequence: ATP8B1 NM_001374385.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120
• Publications: 16 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)

LOC124904310 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP8B1	NM_001374385.1	c.-26+15853C>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.-26+15853C>T		intron_variant	Intron 1 of 27		NM_001374385.1	ENSP00000497896.1

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26346 AN: 151958 Hom.: 2687 Cov.: 32

Gnomad AFR AF: 0.0647

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.0850

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.173 AC: 26343 AN: 152076 Hom.: 2683 Cov.: 32 AF XY: 0.179 AC XY: 13286 AN XY: 74306

African (AFR) AF: 0.0646 AC: 2680 AN: 41508

American (AMR) AF: 0.215 AC: 3283 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 868 AN: 3464

East Asian (EAS) AF: 0.0854 AC: 443 AN: 5186

South Asian (SAS) AF: 0.238 AC: 1149 AN: 4820

European-Finnish (FIN) AF: 0.291 AC: 3062 AN: 10534

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.210 AC: 14281 AN: 67972

Other (OTH) AF: 0.174 AC: 367 AN: 2112

Alfa AF: 0.195 Hom.: 9565

Bravo AF: 0.159

Asia WGS AF: 0.143 AC: 499 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.9
DANN	Benign	0.62
PhyloP100		0.012
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: rs10503019; hg19: chr18-55454377;