chr4-42451236-C-T

Variant names:

• chr4-42451236-C-T
• rs10517025
• NM_006095.2:c.2896+745G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006095.2(ATP8A1):​c.2896+745G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,080 control chromosomes in the GnomAD database, including 2,218 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 0.15 (2218 hom., cov: 31)
• Consequence: ATP8A1 NM_006095.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 11 publications found

Genes affected

ATP8A1 (HGNC:13531): (ATPase phospholipid transporting 8A1) The P-type adenosinetriphosphatases (P-type ATPases) are a family of proteins which use the free energy of ATP hydrolysis to drive uphill transport of ions across membranes. Several subfamilies of P-type ATPases have been identified. One subfamily catalyzes transport of heavy metal ions. Another subfamily transports non-heavy metal ions (NMHI). The protein encoded by this gene is a member of the third subfamily of P-type ATPases and acts to transport amphipaths, such as phosphatidylserine. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

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 = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP8A1	NM_006095.2	c.2896+745G>A		intron_variant	Intron 30 of 36	ENST00000381668.9	NP_006086.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP8A1	ENST00000381668.9	c.2896+745G>A		intron_variant	Intron 30 of 36	1	NM_006095.2	ENSP00000371084.5

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23359 AN: 151960 Hom.: 2220 Cov.: 31

Gnomad AFR AF: 0.0381

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.154 AC: 23355 AN: 152080 Hom.: 2218 Cov.: 31 AF XY: 0.153 AC XY: 11396 AN XY: 74316

African (AFR) AF: 0.0381 AC: 1581 AN: 41518

American (AMR) AF: 0.188 AC: 2864 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 586 AN: 3470

East Asian (EAS) AF: 0.226 AC: 1162 AN: 5152

South Asian (SAS) AF: 0.237 AC: 1141 AN: 4822

European-Finnish (FIN) AF: 0.151 AC: 1594 AN: 10566

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.203 AC: 13801 AN: 67968

Other (OTH) AF: 0.157 AC: 332 AN: 2108

Alfa AF: 0.182 Hom.: 5910

Bravo AF: 0.147

Asia WGS AF: 0.206 AC: 716 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	3.3
DANN	Benign	0.63
PhyloP100		-1.1
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: rs10517025; hg19: chr4-42453253;