ENST00000257254.3:n.-99G>A

Variant names:

• chr11-57237334-G-T
• NM_005161.6:c.-330C>A

Variant summary

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

The ENST00000257254.3(APLNR):​n.-330C>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: APLNR ENST00000257254.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.393
• Publications: 0 publications found

Genes affected

APLNR (HGNC:339): (apelin receptor) This gene encodes a member of the G protein-coupled receptor gene family. The encoded protein is related to the angiotensin receptor, but is actually an apelin receptor that inhibits adenylate cyclase activity and plays a counter-regulatory role against the pressure action of angiotensin II by exerting hypertensive effect. It functions in the cardiovascular and central nervous systems, in glucose metabolism, in embryonic and tumor angiogenesis and as a human immunodeficiency virus (HIV-1) coreceptor. Two transcript variants resulting from alternative splicing have been identified. [provided by RefSeq, Jul 2009]

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=-0.71).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APLNR	NM_005161.6	c.-330C>A		upstream_gene_variant		ENST00000606794.2	NP_005152.1
APLNR	NR_027991.2	n.-84C>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APLNR	ENST00000606794.2	c.-330C>A		upstream_gene_variant		6	NM_005161.6	ENSP00000475344.1
APLNR	ENST00000257254.3	n.-330C>A		upstream_gene_variant		1		ENSP00000257254.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 137582 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 68576

African (AFR) AF: 0.00 AC: 0 AN: 4174

American (AMR) AF: 0.00 AC: 0 AN: 5340

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4580

East Asian (EAS) AF: 0.00 AC: 0 AN: 9340

South Asian (SAS) AF: 0.00 AC: 0 AN: 3066

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22442

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 638

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 79574

Other (OTH) AF: 0.00 AC: 0 AN: 8428

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	15
DANN	Benign	0.65
PhyloP100		0.39
PromoterAI		-0.17	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr11-57004808;