rs930956

Positions:

• chr4-42654326-G-C
• chr4-42654326-G-T

Variant summary

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

The NM_006095.2(ATP8A1):​c.49+2499C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 151,962 control chromosomes in the GnomAD database, including 10,392 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 0.35 (10392 hom., cov: 33)
• Consequence: ATP8A1 NM_006095.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00300

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP8A1	NM_006095.2	c.49+2499C>G		intron_variant		ENST00000381668.9	NP_006086.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP8A1	ENST00000381668.9	c.49+2499C>G		intron_variant		1	NM_006095.2	ENSP00000371084.5
ATP8A1	ENST00000264449.14	c.49+2499C>G		intron_variant		1		ENSP00000264449.10
ATP8A1	ENST00000510289.1	c.49+2499C>G		intron_variant		1		ENSP00000426636.1
ATP8A1	ENST00000700470.1	c.49+2499C>G		intron_variant				ENSP00000515003.1

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53555 AN: 151844 Hom.: 10362 Cov.: 33

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.340

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

GnomAD4 genome AF: 0.353 AC: 53639 AN: 151962 Hom.: 10392 Cov.: 33 AF XY: 0.352 AC XY: 26161 AN XY: 74252

Gnomad4 AFR AF: 0.515

Gnomad4 AMR AF: 0.390

Gnomad4 ASJ AF: 0.246

Gnomad4 EAS AF: 0.419

Gnomad4 SAS AF: 0.373

Gnomad4 FIN AF: 0.248

Gnomad4 NFE AF: 0.259

Gnomad4 OTH AF: 0.345

Alfa AF: 0.295 Hom.: 1073

Bravo AF: 0.375

Asia WGS AF: 0.417 AC: 1450 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.43
DANN	Benign	0.60

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: rs930956; hg19: chr4-42656343;