chr15-50113986-A-G

Variant names:

• chr15-50113986-A-G
• rs4143837
• NM_024837.4:c.-43+5137T>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.-43+5137T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 151,096 control chromosomes in the GnomAD database, including 11,770 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 0.39 (11770 hom., cov: 28)
• Consequence: ATP8B4 NM_024837.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.388
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP8B4	NM_024837.4	c.-43+5137T>C		intron_variant	Intron 1 of 27	ENST00000284509.11	NP_079113.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP8B4	ENST00000284509.11	c.-43+5137T>C		intron_variant	Intron 1 of 27	5	NM_024837.4	ENSP00000284509.6

Frequencies

GnomAD3 genomes AF: 0.388 AC: 58653 AN: 150994 Hom.: 11764 Cov.: 28

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.387

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

GnomAD4 genome AF: 0.388 AC: 58677 AN: 151096 Hom.: 11770 Cov.: 28 AF XY: 0.393 AC XY: 28974 AN XY: 73698

African (AFR) AF: 0.372 AC: 15310 AN: 41184

American (AMR) AF: 0.448 AC: 6802 AN: 15170

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 935 AN: 3464

East Asian (EAS) AF: 0.656 AC: 3388 AN: 5166

South Asian (SAS) AF: 0.394 AC: 1891 AN: 4802

European-Finnish (FIN) AF: 0.419 AC: 4290 AN: 10250

Middle Eastern (MID) AF: 0.248 AC: 72 AN: 290

European-Non Finnish (NFE) AF: 0.366 AC: 24805 AN: 67758

Other (OTH) AF: 0.387 AC: 813 AN: 2100

Alfa AF: 0.375 Hom.: 21336

Bravo AF: 0.395

Asia WGS AF: 0.498 AC: 1727 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.9
DANN	Benign	0.30
PhyloP100		0.39
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: rs4143837; hg19: chr15-50406183; COSMIC: COSV52710662; COSMIC: COSV52710662;