4-42549147-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006095.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP8A1	NM_006095.2	MANE Select	c.1603-85A>G		intron	N/A	NP_006086.1	Q9Y2Q0-1
	ATP8A1	NM_001400024.1		c.1603-85A>G		intron	N/A	NP_001386953.1
	ATP8A1	NM_001400025.1		c.1558-85A>G		intron	N/A	NP_001386954.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP8A1	ENST00000381668.9	TSL:1 MANE Select	c.1603-85A>G		intron	N/A	ENSP00000371084.5	Q9Y2Q0-1
	ATP8A1	ENST00000264449.14	TSL:1	c.1558-85A>G		intron	N/A	ENSP00000264449.10	Q9Y2Q0-3
	ATP8A1	ENST00000905753.1		c.1603-85A>G		intron	N/A	ENSP00000575812.1

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

African (AFR) AF: 0.0279 AC: 603 AN: 21604

American (AMR) AF: 0.192 AC: 5350 AN: 27876

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 2909 AN: 19858

East Asian (EAS) AF: 0.230 AC: 8144 AN: 35358

South Asian (SAS) AF: 0.247 AC: 15492 AN: 62630

European-Finnish (FIN) AF: 0.119 AC: 5949 AN: 49870

Middle Eastern (MID) AF: 0.162 AC: 731 AN: 4502

European-Non Finnish (NFE) AF: 0.164 AC: 112793 AN: 686572

Other (OTH) AF: 0.161 AC: 6759 AN: 42058

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

African (AFR) AF: 0.0331 AC: 1375 AN: 41562

American (AMR) AF: 0.180 AC: 2750 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 495 AN: 3470

East Asian (EAS) AF: 0.256 AC: 1324 AN: 5168

South Asian (SAS) AF: 0.244 AC: 1175 AN: 4816

European-Finnish (FIN) AF: 0.111 AC: 1170 AN: 10574

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.173 AC: 11783 AN: 68012

Other (OTH) AF: 0.145 AC: 307 AN: 2114

Alfa AF: 0.154 Hom.: 1079

Bravo AF: 0.133

Asia WGS AF: 0.212 AC: 738 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.9
DANN	Benign	0.57
PhyloP100		0.050
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: rs3811769; hg19: chr4-42551164;