chr15-50018938-C-A

Variant names:

• chr15-50018938-C-A
• rs12591825
• NM_024837.4:c.363-8021G>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.363-8021G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 1,230,510 control chromosomes in the GnomAD database, including 158,779 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 0.58 (27071 hom., cov: 33)
  • Exomes 𝑓: 0.47 (131708 hom.)
• Consequence: ATP8B4 NM_024837.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.266
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP8B4	NM_024837.4	MANE Select	c.363-8021G>T		intron	N/A	NP_079113.2
	ATP8B4	NR_073596.2		n.554G>T		non_coding_transcript_exon	Exon 7 of 28
	ATP8B4	NR_073598.2		n.625G>T		non_coding_transcript_exon	Exon 7 of 29

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP8B4	ENST00000284509.11	TSL:5 MANE Select	c.363-8021G>T		intron	N/A	ENSP00000284509.6	Q8TF62
	ATP8B4	ENST00000558906.5	TSL:1	n.*32G>T		non_coding_transcript_exon	Exon 7 of 28	ENSP00000452956.1	H0YLJ1
	ATP8B4	ENST00000559726.5	TSL:1	n.*32G>T		non_coding_transcript_exon	Exon 7 of 29	ENSP00000453229.1	H0YLJ1

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87879 AN: 151948 Hom.: 27022 Cov.: 33

Gnomad AFR AF: 0.726

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.603

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.993

Gnomad SAS AF: 0.751

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.543

GnomAD2 exomes AF: 0.608 AC: 77813 AN: 127984 AF XY: 0.605

Gnomad AFR exome AF: 0.725

Gnomad AMR exome AF: 0.705

Gnomad ASJ exome AF: 0.400

Gnomad EAS exome AF: 0.998

Gnomad FIN exome AF: 0.496

Gnomad NFE exome AF: 0.452

Gnomad OTH exome AF: 0.513

GnomAD4 exome AF: 0.475 AC: 511781 AN: 1078444 Hom.: 131708 Cov.: 28 AF XY: 0.483 AC XY: 256781 AN XY: 531492

African (AFR) AF: 0.731 AC: 16640 AN: 22770

American (AMR) AF: 0.706 AC: 19871 AN: 28158

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 6142 AN: 15638

East Asian (EAS) AF: 0.996 AC: 12366 AN: 12418

South Asian (SAS) AF: 0.730 AC: 54423 AN: 74572

European-Finnish (FIN) AF: 0.494 AC: 6232 AN: 12616

Middle Eastern (MID) AF: 0.467 AC: 1996 AN: 4278

European-Non Finnish (NFE) AF: 0.431 AC: 374153 AN: 868648

Other (OTH) AF: 0.507 AC: 19958 AN: 39346

GnomAD4 genome AF: 0.579 AC: 87992 AN: 152066 Hom.: 27071 Cov.: 33 AF XY: 0.586 AC XY: 43584 AN XY: 74318

African (AFR) AF: 0.726 AC: 30149 AN: 41506

American (AMR) AF: 0.604 AC: 9228 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 1409 AN: 3470

East Asian (EAS) AF: 0.993 AC: 5145 AN: 5180

South Asian (SAS) AF: 0.750 AC: 3618 AN: 4824

European-Finnish (FIN) AF: 0.510 AC: 5364 AN: 10526

Middle Eastern (MID) AF: 0.538 AC: 157 AN: 292

European-Non Finnish (NFE) AF: 0.461 AC: 31300 AN: 67968

Other (OTH) AF: 0.548 AC: 1155 AN: 2106

Alfa AF: 0.512 Hom.: 4710

Bravo AF: 0.588

Asia WGS AF: 0.870 AC: 3017 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.49
PhyloP100		-0.27
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: rs12591825; hg19: chr15-50311135; COSMIC: COSV52723174;