NM_024837.4:c.749-664T>G

Variant names:

• chr15-49981958-A-C
• rs16963141
• NM_024837.4:c.749-664T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024837.4(ATP8B4):​c.749-664T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,212 control chromosomes in the GnomAD database, including 1,987 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 (1987 hom., cov: 32)
• Consequence: ATP8B4 NM_024837.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.255
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.213 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP8B4	NM_024837.4	MANE Select	c.749-664T>G		intron	N/A	NP_079113.2
	ATP8B4	NR_073596.2		n.990-664T>G		intron	N/A
	ATP8B4	NR_073597.2		n.902-664T>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP8B4	ENST00000284509.11	TSL:5 MANE Select	c.749-664T>G		intron	N/A	ENSP00000284509.6	Q8TF62
	ATP8B4	ENST00000557955.5	TSL:1	n.749-664T>G		intron	N/A	ENSP00000453690.1	H0YMP8
	ATP8B4	ENST00000558906.5	TSL:1	n.*468-664T>G		intron	N/A	ENSP00000452956.1	H0YLJ1

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23482 AN: 152094 Hom.: 1985 Cov.: 32

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.0886

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.154 AC: 23503 AN: 152212 Hom.: 1987 Cov.: 32 AF XY: 0.149 AC XY: 11120 AN XY: 74432

African (AFR) AF: 0.217 AC: 9016 AN: 41542

American (AMR) AF: 0.117 AC: 1781 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 477 AN: 3470

East Asian (EAS) AF: 0.00231 AC: 12 AN: 5192

South Asian (SAS) AF: 0.133 AC: 642 AN: 4826

European-Finnish (FIN) AF: 0.0886 AC: 940 AN: 10606

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10057 AN: 67976

Other (OTH) AF: 0.140 AC: 296 AN: 2112

Alfa AF: 0.168 Hom.: 314

Bravo AF: 0.158

Asia WGS AF: 0.0690 AC: 239 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.60
PhyloP100		-0.26
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: rs16963141; hg19: chr15-50274155;