ENST00000557955.5:n.*1394A>C

Variant names:

• chr15-49860077-T-G
• rs4494483
• ENST00000557955.5:n.*1394A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000557955.5(ATP8B4):​n.*1394A>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 0.00000176 in 1,135,364 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: ATP8B4 ENST00000557955.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.69
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000557955.5. 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.*117A>C		3_prime_UTR	Exon 28 of 28	NP_079113.2
	ATP8B4	NR_073596.2		n.3748A>C		non_coding_transcript_exon	Exon 28 of 28
	ATP8B4	NR_073597.2		n.3701A>C		non_coding_transcript_exon	Exon 27 of 27

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP8B4	ENST00000557955.5	TSL:1	n.*1394A>C		non_coding_transcript_exon	Exon 27 of 27	ENSP00000453690.1
	ATP8B4	ENST00000558498.5	TSL:1	n.968A>C		non_coding_transcript_exon	Exon 5 of 5
	ATP8B4	ENST00000558906.5	TSL:1	n.*3226A>C		non_coding_transcript_exon	Exon 28 of 28	ENSP00000452956.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000176 AC: 2 AN: 1135364 Hom.: 0 Cov.: 16 AF XY: 0.00000177 AC XY: 1 AN XY: 566446

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 25724

American (AMR) AF: 0.00 AC: 0 AN: 28638

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18738

East Asian (EAS) AF: 0.00 AC: 0 AN: 37768

South Asian (SAS) AF: 0.0000156 AC: 1 AN: 64040

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38098

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4874

European-Non Finnish (NFE) AF: 0.00000115 AC: 1 AN: 868602

Other (OTH) AF: 0.00 AC: 0 AN: 48882

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0385499), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.074
DANN	Benign	0.75
PhyloP100		-2.7

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: rs4494483; hg19: chr15-50152274;