chr15-49972335-T-C

Position:

• chr15-49972335-T-C

Variant summary

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

The NM_024837.4(ATP8B4):​c.1243+247A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.736 in 152,002 control chromosomes in the GnomAD database, including 42,825 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 0.74 (42825 hom., cov: 30)
• Consequence: ATP8B4 NM_024837.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.577

Genes affected

ATP8B4 (HGNC:13536): (ATPase phospholipid transporting 8B4 (putative)) This gene encodes a member of the cation transport ATPase (P-type) family and type IV subfamily. The encoded protein is involved in phospholipid transport in the cell membrane. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP8B4	NM_024837.4	c.1243+247A>G		intron_variant		ENST00000284509.11	NP_079113.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP8B4	ENST00000284509.11	c.1243+247A>G		intron_variant		5	NM_024837.4	ENSP00000284509	P1

Frequencies

GnomAD3 genomes AF: 0.736 AC: 111737 AN: 151884 Hom.: 42749 Cov.: 30

Gnomad AFR AF: 0.930

Gnomad AMI AF: 0.686

Gnomad AMR AF: 0.755

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.800

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.620

Gnomad OTH AF: 0.709

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

GnomAD4 genome AF: 0.736 AC: 111880 AN: 152002 Hom.: 42825 Cov.: 30 AF XY: 0.737 AC XY: 54782 AN XY: 74300

Gnomad4 AFR AF: 0.930

Gnomad4 AMR AF: 0.756

Gnomad4 ASJ AF: 0.620

Gnomad4 EAS AF: 0.995

Gnomad4 SAS AF: 0.800

Gnomad4 FIN AF: 0.585

Gnomad4 NFE AF: 0.620

Gnomad4 OTH AF: 0.713

Alfa AF: 0.665 Hom.: 24558

Bravo AF: 0.755

Asia WGS AF: 0.915 AC: 3177 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.1
DANN	Benign	0.71

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: rs12593937; hg19: chr15-50264532;