15-49905673-A-G

Variant names:

• chr15-49905673-A-G
• rs12440932
• NM_024837.4:c.2142-4434T>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.2142-4434T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0457 in 152,246 control chromosomes in the GnomAD database, including 638 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 0.046 (638 hom., cov: 32)
• Consequence: ATP8B4 NM_024837.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.94
• 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=-0.61).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.407 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.2142-4434T>C		intron	N/A	NP_079113.2
	ATP8B4	NR_073596.2		n.2194-4434T>C		intron	N/A
	ATP8B4	NR_073597.2		n.2295-7422T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP8B4	ENST00000284509.11	TSL:5 MANE Select	c.2142-4434T>C		intron	N/A	ENSP00000284509.6
	ATP8B4	ENST00000557955.5	TSL:1	n.2142-7422T>C		intron	N/A	ENSP00000453690.1
	ATP8B4	ENST00000558906.5	TSL:1	n.*1672-4434T>C		intron	N/A	ENSP00000452956.1

Frequencies

GnomAD3 genomes AF: 0.0458 AC: 6960 AN: 152128 Hom.: 639 Cov.: 32

Gnomad AFR AF: 0.00900

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0884

Gnomad ASJ AF: 0.0127

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.0605

Gnomad FIN AF: 0.0595

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0291

Gnomad OTH AF: 0.0363

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

GnomAD4 genome AF: 0.0457 AC: 6960 AN: 152246 Hom.: 638 Cov.: 32 AF XY: 0.0507 AC XY: 3772 AN XY: 74444

African (AFR) AF: 0.00897 AC: 373 AN: 41564

American (AMR) AF: 0.0888 AC: 1358 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0127 AC: 44 AN: 3470

East Asian (EAS) AF: 0.422 AC: 2183 AN: 5174

South Asian (SAS) AF: 0.0599 AC: 289 AN: 4826

European-Finnish (FIN) AF: 0.0595 AC: 631 AN: 10604

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0291 AC: 1980 AN: 68000

Other (OTH) AF: 0.0355 AC: 75 AN: 2114

Alfa AF: 0.0334 Hom.: 81

Bravo AF: 0.0458

Asia WGS AF: 0.191 AC: 661 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	18
DANN	Benign	0.83
PhyloP100		2.9
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: rs12440932; hg19: chr15-50197870;