rs4375601

Variant names:

• chr15-49879650-C-T
• rs4375601
• NM_024837.4:c.2698-191G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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]

ENSG00000259188 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ATP8B4	NM_024837.4	c.2698-191G>A		intron_variant	Intron 23 of 27	ENST00000284509.11	NP_079113.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP8B4	ENST00000284509.11	c.2698-191G>A		intron_variant	Intron 23 of 27	5	NM_024837.4	ENSP00000284509.6

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

African (AFR) AF: 0.155 AC: 1504 AN: 9706

American (AMR) AF: 0.103 AC: 1332 AN: 12938

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 1780 AN: 12036

East Asian (EAS) AF: 0.0435 AC: 1137 AN: 26154

South Asian (SAS) AF: 0.253 AC: 8761 AN: 34674

European-Finnish (FIN) AF: 0.153 AC: 4896 AN: 32018

Middle Eastern (MID) AF: 0.110 AC: 188 AN: 1712

European-Non Finnish (NFE) AF: 0.159 AC: 37557 AN: 236486

Other (OTH) AF: 0.155 AC: 3445 AN: 22232

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

African (AFR) AF: 0.156 AC: 6416 AN: 41236

American (AMR) AF: 0.111 AC: 1682 AN: 15186

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 546 AN: 3462

East Asian (EAS) AF: 0.0738 AC: 381 AN: 5166

South Asian (SAS) AF: 0.263 AC: 1258 AN: 4784

European-Finnish (FIN) AF: 0.137 AC: 1435 AN: 10500

Middle Eastern (MID) AF: 0.0822 AC: 24 AN: 292

European-Non Finnish (NFE) AF: 0.159 AC: 10813 AN: 67888

Other (OTH) AF: 0.150 AC: 315 AN: 2100

Alfa AF: 0.154 Hom.: 2817

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
PhyloP100		-0.72
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: rs4375601; hg19: chr15-50171847; COSMIC: COSV52726445; COSMIC: COSV52726445;