Genetic Variant ATP8B4:n.*1502A>C (chr15-49859969-T-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000557955.5(ATP8B4):n.*1502A>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 0.00000913 in 328,412 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: 0.0000091 ( 0 hom. )

Consequence

ATP8B4
ENST00000557955.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.489

Publications

7 publications found

Variant links:

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]

ATP8B4 links:

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ACMG classification

Classification was made for transcript

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=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP8B4	NM_024837.4 link	c.*225A>C		3_prime_UTR_variant	Exon 28 of 28	ENST00000284509.11	NP_079113.2	Q8TF62Q6PG43

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP8B4	ENST00000284509.11 link	c.*225A>C		3_prime_UTR_variant	Exon 28 of 28	5	NM_024837.4	ENSP00000284509.6		Q8TF62

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000913

AC:

AN:

328412

Hom.:

Cov.:

AF XY:

0.00000594

AC XY:

AN XY:

168214

show subpopulations

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

African (AFR)

AF:

0.000112

AC:

AN:

8942

American (AMR)

AF:

0.00

AC:

AN:

10824

Ashkenazi Jewish (ASJ)

AF:

0.0000934

AC:

AN:

10708

East Asian (EAS)

AF:

0.00

AC:

AN:

25498

South Asian (SAS)

AF:

0.00

AC:

AN:

15436

European-Finnish (FIN)

AF:

0.00

AC:

AN:

23688

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1608

European-Non Finnish (NFE)

AF:

0.00000473

AC:

AN:

211598

Other (OTH)

AF:

0.00

AC:

AN:

20110

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

646

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.5

(source)

DANN

Benign

0.59

PhyloP100

-0.49

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over