4-42509225-C-T

Position:

• chr4-42509225-C-T

Variant summary

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

The ENST00000381668.9(ATP8A1):​c.1948-2071G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 152,220 control chromosomes in the GnomAD database, including 1,690 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 0.13 (1690 hom., cov: 32)
• Consequence: ATP8A1 ENST00000381668.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.61

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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP8A1	NM_006095.2	c.1948-2071G>A		intron_variant		ENST00000381668.9	NP_006086.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP8A1	ENST00000381668.9	c.1948-2071G>A		intron_variant		1	NM_006095.2	ENSP00000371084	A1
ATP8A1	ENST00000264449.14	c.1903-2071G>A		intron_variant		1		ENSP00000264449	P3
ATP8A1	ENST00000700470.1	c.1903-2071G>A		intron_variant				ENSP00000515003	A1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20191 AN: 152102 Hom.: 1694 Cov.: 32

Gnomad AFR AF: 0.0319

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.133 AC: 20189 AN: 152220 Hom.: 1690 Cov.: 32 AF XY: 0.133 AC XY: 9935 AN XY: 74430

Gnomad4 AFR AF: 0.0319

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.156

Gnomad4 EAS AF: 0.258

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.145

Alfa AF: 0.159 Hom.: 2770

Bravo AF: 0.130

Asia WGS AF: 0.207 AC: 720 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.22
DANN	Benign	0.76

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: rs10517038; hg19: chr4-42511242;