15-49900780-G-A

Variant names:

• chr15-49900780-G-A
• rs2899440
• NM_024837.4:c.2289+312C>T

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+312C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 151,922 control chromosomes in the GnomAD database, including 17,898 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 0.48 (17898 hom., cov: 32)
• Consequence: ATP8B4 NM_024837.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.331
• Publications: 1 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024837.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP8B4	NM_024837.4	MANE Select	c.2289+312C>T		intron	N/A	NP_079113.2
	ATP8B4	NR_073596.2		n.2341+312C>T		intron	N/A
	ATP8B4	NR_073597.2		n.2295-2529C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP8B4	ENST00000284509.11	TSL:5 MANE Select	c.2289+312C>T		intron	N/A	ENSP00000284509.6
	ATP8B4	ENST00000557955.5	TSL:1	n.2142-2529C>T		intron	N/A	ENSP00000453690.1
	ATP8B4	ENST00000558906.5	TSL:1	n.*1819+312C>T		intron	N/A	ENSP00000452956.1

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72420 AN: 151804 Hom.: 17883 Cov.: 32

Gnomad AFR AF: 0.606

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.479

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

GnomAD4 genome AF: 0.477 AC: 72483 AN: 151922 Hom.: 17898 Cov.: 32 AF XY: 0.478 AC XY: 35495 AN XY: 74262

African (AFR) AF: 0.606 AC: 25104 AN: 41422

American (AMR) AF: 0.373 AC: 5694 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.415 AC: 1442 AN: 3472

East Asian (EAS) AF: 0.497 AC: 2568 AN: 5166

South Asian (SAS) AF: 0.512 AC: 2462 AN: 4812

European-Finnish (FIN) AF: 0.482 AC: 5083 AN: 10546

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.420 AC: 28548 AN: 67924

Other (OTH) AF: 0.482 AC: 1018 AN: 2114

Alfa AF: 0.426 Hom.: 19231

Bravo AF: 0.472

Asia WGS AF: 0.521 AC: 1812 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.8
DANN	Benign	0.51
PhyloP100		0.33
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: rs2899440; hg19: chr15-50192977;