chr15-49974927-C-T

Position:

• chr15-49974927-C-T

Variant summary

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

The NM_024837.4(ATP8B4):​c.1035-2137G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.736 in 152,078 control chromosomes in the GnomAD database, including 42,806 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 0.74 (42806 hom., cov: 32)
• Consequence: ATP8B4 NM_024837.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00400

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP8B4	NM_024837.4	c.1035-2137G>A		intron_variant		ENST00000284509.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP8B4	ENST00000284509.11	c.1035-2137G>A		intron_variant		5	NM_024837.4	P1

Frequencies

GnomAD3 genomes AF: 0.735 AC: 111752 AN: 151956 Hom.: 42729 Cov.: 32

Gnomad AFR AF: 0.929

Gnomad AMI AF: 0.685

Gnomad AMR AF: 0.753

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.800

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.631

Gnomad NFE AF: 0.620

Gnomad OTH AF: 0.709

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

GnomAD4 genome AF: 0.736 AC: 111897 AN: 152078 Hom.: 42806 Cov.: 32 AF XY: 0.737 AC XY: 54778 AN XY: 74310

Gnomad4 AFR AF: 0.930

Gnomad4 AMR AF: 0.753

Gnomad4 ASJ AF: 0.621

Gnomad4 EAS AF: 0.995

Gnomad4 SAS AF: 0.800

Gnomad4 FIN AF: 0.585

Gnomad4 NFE AF: 0.620

Gnomad4 OTH AF: 0.713

Alfa AF: 0.684 Hom.: 4589

Bravo AF: 0.754

Asia WGS AF: 0.916 AC: 3160 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.8
DANN	Benign	0.50

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: rs8036322; hg19: chr15-50267124; COSMIC: COSV52716749; COSMIC: COSV52716749;