NM_024837.4:c.-42-441T>C

Variant names:

• chr15-50107449-A-G
• rs11639262
• NM_024837.4:c.-42-441T>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.-42-441T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,192 control chromosomes in the GnomAD database, including 1,463 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 0.13 (1463 hom., cov: 32)
• Consequence: ATP8B4 NM_024837.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0820
• 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024837.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP8B4	NM_024837.4	MANE Select	c.-42-441T>C		intron	N/A	NP_079113.2
	ATP8B4	NR_073596.2		n.112-441T>C		intron	N/A
	ATP8B4	NR_073597.2		n.112-441T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP8B4	ENST00000284509.11	TSL:5 MANE Select	c.-42-441T>C		intron	N/A	ENSP00000284509.6
	ATP8B4	ENST00000557955.5	TSL:1	n.-42-441T>C		intron	N/A	ENSP00000453690.1
	ATP8B4	ENST00000558906.5	TSL:1	n.-42-441T>C		intron	N/A	ENSP00000452956.1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20389 AN: 152074 Hom.: 1461 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.0492

Gnomad SAS AF: 0.0968

Gnomad FIN AF: 0.0768

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.162

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

GnomAD4 genome AF: 0.134 AC: 20405 AN: 152192 Hom.: 1463 Cov.: 32 AF XY: 0.130 AC XY: 9658 AN XY: 74410

African (AFR) AF: 0.148 AC: 6162 AN: 41522

American (AMR) AF: 0.136 AC: 2086 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 742 AN: 3472

East Asian (EAS) AF: 0.0491 AC: 254 AN: 5176

South Asian (SAS) AF: 0.0967 AC: 466 AN: 4818

European-Finnish (FIN) AF: 0.0768 AC: 814 AN: 10600

Middle Eastern (MID) AF: 0.158 AC: 46 AN: 292

European-Non Finnish (NFE) AF: 0.139 AC: 9477 AN: 68002

Other (OTH) AF: 0.160 AC: 339 AN: 2114

Alfa AF: 0.143 Hom.: 2973

Bravo AF: 0.141

Asia WGS AF: 0.0760 AC: 263 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.4
DANN	Benign	0.72
PhyloP100		-0.082
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: rs11639262; hg19: chr15-50399646;