15-49920084-A-G

Variant names:

• chr15-49920084-A-G
• rs16963076
• NM_024837.4:c.1923+162T>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.1923+162T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 152,178 control chromosomes in the GnomAD database, including 5,733 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 0.23 (5733 hom., cov: 32)
• Consequence: ATP8B4 NM_024837.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.241
• Publications: 0 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.456 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.1923+162T>C		intron	N/A	NP_079113.2
	ATP8B4	NR_073596.2		n.1975+162T>C		intron	N/A
	ATP8B4	NR_073597.2		n.2076+162T>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.1923+162T>C		intron	N/A	ENSP00000284509.6
	ATP8B4	ENST00000557955.5	TSL:1	n.1923+162T>C		intron	N/A	ENSP00000453690.1
	ATP8B4	ENST00000558906.5	TSL:1	n.*1453+162T>C		intron	N/A	ENSP00000452956.1

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34806 AN: 152060 Hom.: 5729 Cov.: 32

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.0950

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.229 AC: 34850 AN: 152178 Hom.: 5733 Cov.: 32 AF XY: 0.221 AC XY: 16435 AN XY: 74404

African (AFR) AF: 0.461 AC: 19126 AN: 41474

American (AMR) AF: 0.146 AC: 2229 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 557 AN: 3470

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5182

South Asian (SAS) AF: 0.122 AC: 587 AN: 4826

European-Finnish (FIN) AF: 0.0950 AC: 1008 AN: 10616

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.156 AC: 10636 AN: 68004

Other (OTH) AF: 0.188 AC: 398 AN: 2114

Alfa AF: 0.101 Hom.: 194

Bravo AF: 0.242

Asia WGS AF: 0.0760 AC: 264 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.28
DANN	Benign	0.57
PhyloP100		-0.24
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: rs16963076; hg19: chr15-50212281;