rs16963067

Variant names:

• chr15-49917061-T-C
• rs16963067
• NM_024837.4:c.2036-22A>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.2036-22A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 1,606,320 control chromosomes in the GnomAD database, including 26,435 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 (5881 hom., cov: 32)
  • Exomes 𝑓: 0.16 (20554 hom.)
• Consequence: ATP8B4 NM_024837.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.869
• Publications: 6 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 = 0.463 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.2036-22A>G		intron	N/A	NP_079113.2
	ATP8B4	NR_073596.2		n.2088-22A>G		intron	N/A
	ATP8B4	NR_073597.2		n.2189-22A>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.2036-22A>G		intron	N/A	ENSP00000284509.6	Q8TF62
	ATP8B4	ENST00000557955.5	TSL:1	n.2036-22A>G		intron	N/A	ENSP00000453690.1	H0YMP8
	ATP8B4	ENST00000558906.5	TSL:1	n.*1566-22A>G		intron	N/A	ENSP00000452956.1	H0YLJ1

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35219 AN: 152024 Hom.: 5875 Cov.: 32

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.00192

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.0907

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.195

GnomAD2 exomes AF: 0.149 AC: 37306 AN: 250682 AF XY: 0.146

Gnomad AFR exome AF: 0.478

Gnomad AMR exome AF: 0.0950

Gnomad ASJ exome AF: 0.155

Gnomad EAS exome AF: 0.00136

Gnomad FIN exome AF: 0.0954

Gnomad NFE exome AF: 0.154

Gnomad OTH exome AF: 0.148

GnomAD4 exome AF: 0.156 AC: 227573 AN: 1454178 Hom.: 20554 Cov.: 29 AF XY: 0.157 AC XY: 113410 AN XY: 723984

African (AFR) AF: 0.486 AC: 16188 AN: 33296

American (AMR) AF: 0.102 AC: 4539 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 3869 AN: 26092

East Asian (EAS) AF: 0.00103 AC: 41 AN: 39654

South Asian (SAS) AF: 0.143 AC: 12287 AN: 85976

European-Finnish (FIN) AF: 0.0988 AC: 5256 AN: 53192

Middle Eastern (MID) AF: 0.163 AC: 935 AN: 5748

European-Non Finnish (NFE) AF: 0.158 AC: 174783 AN: 1105352

Other (OTH) AF: 0.161 AC: 9675 AN: 60196

GnomAD4 genome AF: 0.232 AC: 35264 AN: 152142 Hom.: 5881 Cov.: 32 AF XY: 0.224 AC XY: 16631 AN XY: 74386

African (AFR) AF: 0.469 AC: 19449 AN: 41478

American (AMR) AF: 0.147 AC: 2251 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 561 AN: 3466

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5186

South Asian (SAS) AF: 0.132 AC: 637 AN: 4818

European-Finnish (FIN) AF: 0.0907 AC: 963 AN: 10612

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

European-Non Finnish (NFE) AF: 0.157 AC: 10695 AN: 67986

Other (OTH) AF: 0.192 AC: 403 AN: 2104

Alfa AF: 0.197 Hom.: 734

Bravo AF: 0.246

Asia WGS AF: 0.0790 AC: 275 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	0.24
DANN	Benign	0.46
PhyloP100		-0.87
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: rs16963067; hg19: chr15-50209258;