rs16963141

chr15-49981958-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024837.4(ATP8B4):c.749-664T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,212 control chromosomes in the GnomAD database, including 1,987 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 0.15 (1987 hom., cov: 32)
• Consequence: ATP8B4 NM_024837.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.255

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP8B4	NM_024837.4	c.749-664T>G		intron_variant		ENST00000284509.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP8B4	ENST00000284509.11	c.749-664T>G		intron_variant		5	NM_024837.4	P1

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23482 AN: 152094 Hom.: 1985 Cov.: 32

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.0886

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.154 AC: 23503 AN: 152212 Hom.: 1987 Cov.: 32 AF XY: 0.149 AC XY: 11120 AN XY: 74432

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.117

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.00231

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.0886

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.140

Alfa AF: 0.166 Hom.: 296

Bravo AF: 0.158

Asia WGS AF: 0.0690 AC: 239 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.8
Dann	Benign	0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs16963141; hg19: chr15-50274155;