rs16963180

Variant names:

• chr15-50004855-A-C
• rs16963180
• NM_024837.4:c.436-2632T>G

Variant summary

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

The NM_024837.4(ATP8B4):​c.436-2632T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0664 in 152,230 control chromosomes in the GnomAD database, including 364 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 0.066 (364 hom., cov: 32)
• Consequence: ATP8B4 NM_024837.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.653
• Publications: 0 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP8B4	NM_024837.4	c.436-2632T>G		intron_variant	Intron 7 of 27	ENST00000284509.11	NP_079113.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP8B4	ENST00000284509.11	c.436-2632T>G		intron_variant	Intron 7 of 27	5	NM_024837.4	ENSP00000284509.6

Frequencies

GnomAD3 genomes AF: 0.0664 AC: 10097 AN: 152112 Hom.: 365 Cov.: 32

Gnomad AFR AF: 0.0547

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.0540

Gnomad ASJ AF: 0.0594

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0294

Gnomad FIN AF: 0.0532

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0853

Gnomad OTH AF: 0.0568

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

GnomAD4 genome AF: 0.0664 AC: 10105 AN: 152230 Hom.: 364 Cov.: 32 AF XY: 0.0639 AC XY: 4754 AN XY: 74426

African (AFR) AF: 0.0547 AC: 2272 AN: 41540

American (AMR) AF: 0.0539 AC: 824 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0594 AC: 206 AN: 3466

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5188

South Asian (SAS) AF: 0.0298 AC: 144 AN: 4828

European-Finnish (FIN) AF: 0.0532 AC: 564 AN: 10600

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0853 AC: 5803 AN: 68006

Other (OTH) AF: 0.0558 AC: 118 AN: 2116

Alfa AF: 0.0780 Hom.: 57

Bravo AF: 0.0662

Asia WGS AF: 0.0190 AC: 66 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.5
DANN	Benign	0.80
PhyloP100		0.65
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: rs16963180; hg19: chr15-50297052;