rs4375601

Positions:

• chr15-49879650-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.2698-191G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 539,480 control chromosomes in the GnomAD database, including 7,021 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 (1836 hom., cov: 31)
  • Exomes 𝑓: 0.16 (5185 hom.)
• Consequence: ATP8B4 NM_024837.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.719

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]

(HGNC:):

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 (SAS) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP8B4	NM_024837.4	c.2698-191G>A		intron_variant		ENST00000284509.11
LOC102724587	XR_932215.3	n.131-669C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP8B4	ENST00000284509.11	c.2698-191G>A		intron_variant		5	NM_024837.4	P1
	ENST00000666846.1	n.131-935C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.152 AC: 22949 AN: 151406 Hom.: 1831 Cov.: 31

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.0736

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.0796

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.145

GnomAD4 exome AF: 0.156 AC: 60600 AN: 387956 Hom.: 5185 Cov.: 4 AF XY: 0.161 AC XY: 32869 AN XY: 204500

Gnomad4 AFR exome AF: 0.155

Gnomad4 AMR exome AF: 0.103

Gnomad4 ASJ exome AF: 0.148

Gnomad4 EAS exome AF: 0.0435

Gnomad4 SAS exome AF: 0.253

Gnomad4 FIN exome AF: 0.153

Gnomad4 NFE exome AF: 0.159

Gnomad4 OTH exome AF: 0.155

GnomAD4 genome AF: 0.152 AC: 22973 AN: 151524 Hom.: 1836 Cov.: 31 AF XY: 0.152 AC XY: 11231 AN XY: 74028

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.0738

Gnomad4 SAS AF: 0.263

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.150

Alfa AF: 0.160 Hom.: 262

Bravo AF: 0.145

Asia WGS AF: 0.232 AC: 805 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.66
DANN	Benign	0.55

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: rs4375601; hg19: chr15-50171847; COSMIC: COSV52726445; COSMIC: COSV52726445;