rs12913008

Variant names:

• chr15-49900815-C-G
• rs12913008
• NM_024837.4:c.2289+277G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024837.4(ATP8B4):​c.2289+277G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 152,054 control chromosomes in the GnomAD database, including 13,679 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 0.41 (13679 hom., cov: 32)
• Consequence: ATP8B4 NM_024837.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0980
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP8B4	NM_024837.4	c.2289+277G>C		intron_variant	Intron 21 of 27	ENST00000284509.11	NP_079113.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP8B4	ENST00000284509.11	c.2289+277G>C		intron_variant	Intron 21 of 27	5	NM_024837.4	ENSP00000284509.6

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62726 AN: 151936 Hom.: 13675 Cov.: 32

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.407

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

GnomAD4 genome AF: 0.413 AC: 62752 AN: 152054 Hom.: 13679 Cov.: 32 AF XY: 0.417 AC XY: 30997 AN XY: 74306

African (AFR) AF: 0.269 AC: 11172 AN: 41498

American (AMR) AF: 0.520 AC: 7926 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 1438 AN: 3470

East Asian (EAS) AF: 0.489 AC: 2528 AN: 5168

South Asian (SAS) AF: 0.359 AC: 1732 AN: 4822

European-Finnish (FIN) AF: 0.500 AC: 5280 AN: 10560

Middle Eastern (MID) AF: 0.421 AC: 123 AN: 292

European-Non Finnish (NFE) AF: 0.461 AC: 31321 AN: 67970

Other (OTH) AF: 0.406 AC: 859 AN: 2114

Alfa AF: 0.434 Hom.: 1840

Bravo AF: 0.414

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.66
PhyloP100		0.098
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: rs12913008; hg19: chr15-50193012;