15-50018951-A-G

Variant names:

• chr15-50018951-A-G
• rs11070741
• ENST00000558906.5:n.*19T>C

Variant summary

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

The ENST00000558906.5(ATP8B4):​n.*19T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 1,225,298 control chromosomes in the GnomAD database, including 212,770 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 0.68 (37561 hom., cov: 32)
  • Exomes 𝑓: 0.56 (175209 hom.)
• Consequence: ATP8B4 ENST00000558906.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.180
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000558906.5. 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.363-8034T>C		intron	N/A	NP_079113.2
	ATP8B4	NR_073596.2		n.541T>C		non_coding_transcript_exon	Exon 7 of 28
	ATP8B4	NR_073598.2		n.612T>C		non_coding_transcript_exon	Exon 7 of 29

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP8B4	ENST00000558906.5	TSL:1	n.*19T>C		non_coding_transcript_exon	Exon 7 of 28	ENSP00000452956.1
	ATP8B4	ENST00000559726.5	TSL:1	n.*19T>C		non_coding_transcript_exon	Exon 7 of 29	ENSP00000453229.1
	ATP8B4	ENST00000558906.5	TSL:1	n.*19T>C		3_prime_UTR	Exon 7 of 28	ENSP00000452956.1

Frequencies

GnomAD3 genomes AF: 0.681 AC: 103457 AN: 151984 Hom.: 37485 Cov.: 32

Gnomad AFR AF: 0.912

Gnomad AMI AF: 0.684

Gnomad AMR AF: 0.667

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.781

Gnomad FIN AF: 0.563

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.543

Gnomad OTH AF: 0.628

GnomAD2 exomes AF: 0.669 AC: 85615 AN: 128010 AF XY: 0.664

Gnomad AFR exome AF: 0.926

Gnomad AMR exome AF: 0.746

Gnomad ASJ exome AF: 0.452

Gnomad EAS exome AF: 0.998

Gnomad FIN exome AF: 0.561

Gnomad NFE exome AF: 0.532

Gnomad OTH exome AF: 0.569

GnomAD4 exome AF: 0.556 AC: 596175 AN: 1073194 Hom.: 175209 Cov.: 28 AF XY: 0.563 AC XY: 297949 AN XY: 529282

African (AFR) AF: 0.931 AC: 21125 AN: 22684

American (AMR) AF: 0.747 AC: 21017 AN: 28152

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 6972 AN: 15616

East Asian (EAS) AF: 0.996 AC: 12330 AN: 12378

South Asian (SAS) AF: 0.766 AC: 57034 AN: 74452

European-Finnish (FIN) AF: 0.554 AC: 6983 AN: 12608

Middle Eastern (MID) AF: 0.517 AC: 2200 AN: 4258

European-Non Finnish (NFE) AF: 0.516 AC: 445644 AN: 863874

Other (OTH) AF: 0.584 AC: 22870 AN: 39172

GnomAD4 genome AF: 0.681 AC: 103600 AN: 152104 Hom.: 37561 Cov.: 32 AF XY: 0.686 AC XY: 50995 AN XY: 74326

African (AFR) AF: 0.912 AC: 37878 AN: 41526

American (AMR) AF: 0.668 AC: 10212 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 1602 AN: 3470

East Asian (EAS) AF: 0.994 AC: 5159 AN: 5190

South Asian (SAS) AF: 0.780 AC: 3768 AN: 4828

European-Finnish (FIN) AF: 0.563 AC: 5935 AN: 10544

Middle Eastern (MID) AF: 0.599 AC: 175 AN: 292

European-Non Finnish (NFE) AF: 0.543 AC: 36914 AN: 67950

Other (OTH) AF: 0.632 AC: 1333 AN: 2108

Alfa AF: 0.597 Hom.: 5219

Bravo AF: 0.696

Asia WGS AF: 0.902 AC: 3127 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	9.5
DANN	Benign	0.59
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs11070741; hg19: chr15-50311148;