4-42425571-A-G

Position:

• chr4-42425571-A-G

Variant summary

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

The NM_006095.2(ATP8A1):​c.3124-1866T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 151,418 control chromosomes in the GnomAD database, including 11,167 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 0.38 (11167 hom., cov: 30)
• Consequence: ATP8A1 NM_006095.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.363

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP8A1	NM_006095.2	c.3124-1866T>C		intron_variant		ENST00000381668.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP8A1	ENST00000381668.9	c.3124-1866T>C		intron_variant		1	NM_006095.2	A1

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57339 AN: 151298 Hom.: 11153 Cov.: 30

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.381

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

GnomAD4 genome AF: 0.379 AC: 57377 AN: 151418 Hom.: 11167 Cov.: 30 AF XY: 0.380 AC XY: 28116 AN XY: 73978

Gnomad4 AFR AF: 0.462

Gnomad4 AMR AF: 0.401

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.149

Gnomad4 SAS AF: 0.325

Gnomad4 FIN AF: 0.390

Gnomad4 NFE AF: 0.344

Gnomad4 OTH AF: 0.382

Alfa AF: 0.173 Hom.: 264

Bravo AF: 0.383

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.087
DANN	Benign	0.34

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: rs10019985; hg19: chr4-42427588;