4-42549147-T-C

Variant names:

• chr4-42549147-T-C
• rs3811769
• NM_006095.2:c.1603-85A>G

Variant summary

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

The NM_006095.2(ATP8A1):​c.1603-85A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 1,102,524 control chromosomes in the GnomAD database, including 16,354 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 0.14 (1769 hom., cov: 32)
  • Exomes 𝑓: 0.17 (14585 hom.)
• Consequence: ATP8A1 NM_006095.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0500

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP8A1	NM_006095.2	c.1603-85A>G		intron_variant	Intron 18 of 36	ENST00000381668.9	NP_006086.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP8A1	ENST00000381668.9	c.1603-85A>G		intron_variant	Intron 18 of 36	1	NM_006095.2	ENSP00000371084.5
ATP8A1	ENST00000264449.14	c.1558-85A>G		intron_variant	Intron 17 of 35	1		ENSP00000264449.10
ATP8A1	ENST00000700470.1	c.1558-85A>G		intron_variant	Intron 17 of 35			ENSP00000515003.1

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20666 AN: 152078 Hom.: 1773 Cov.: 32

Gnomad AFR AF: 0.0331

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.145

GnomAD4 exome AF: 0.167 AC: 158730 AN: 950328 Hom.: 14585 AF XY: 0.171 AC XY: 83165 AN XY: 487748

Gnomad4 AFR exome AF: 0.0279

Gnomad4 AMR exome AF: 0.192

Gnomad4 ASJ exome AF: 0.146

Gnomad4 EAS exome AF: 0.230

Gnomad4 SAS exome AF: 0.247

Gnomad4 FIN exome AF: 0.119

Gnomad4 NFE exome AF: 0.164

Gnomad4 OTH exome AF: 0.161

GnomAD4 genome AF: 0.136 AC: 20661 AN: 152196 Hom.: 1769 Cov.: 32 AF XY: 0.136 AC XY: 10139 AN XY: 74406

Gnomad4 AFR AF: 0.0331

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.256

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.111

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.145

Alfa AF: 0.152 Hom.: 966

Bravo AF: 0.133

Asia WGS AF: 0.212 AC: 738 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.9
DANN	Benign	0.57

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: rs3811769; hg19: chr4-42551164;