11-57237103-C-T

Position:

• chr11-57237103-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005161.6(APLNR):​c.-99G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 1,310,254 control chromosomes in the GnomAD database, including 45,287 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 0.22 (3990 hom., cov: 31)
  • Exomes 𝑓: 0.26 (41297 hom.)
• Consequence: APLNR NM_005161.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42

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]

APLNR (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APLNR	NM_005161.6	c.-99G>A		5_prime_UTR_variant	1/1	ENST00000606794.2	NP_005152.1
APLNR	NR_027991.2	n.148G>A		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APLNR	ENST00000606794.2	c.-99G>A		5_prime_UTR_variant	1/1	6	NM_005161.6	ENSP00000475344.1
APLNR	ENST00000257254.3	n.-99G>A		non_coding_transcript_exon_variant	1/2	1		ENSP00000257254.3
APLNR	ENST00000257254.3	n.-99G>A		5_prime_UTR_variant	1/2	1		ENSP00000257254.3

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32741 AN: 151996 Hom.: 3995 Cov.: 31

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.225

GnomAD4 exome AF: 0.264 AC: 306251 AN: 1158138 Hom.: 41297 Cov.: 16 AF XY: 0.263 AC XY: 150499 AN XY: 572930

Gnomad4 AFR exome AF: 0.0937

Gnomad4 AMR exome AF: 0.242

Gnomad4 ASJ exome AF: 0.239

Gnomad4 EAS exome AF: 0.225

Gnomad4 SAS exome AF: 0.215

Gnomad4 FIN exome AF: 0.215

Gnomad4 NFE exome AF: 0.280

Gnomad4 OTH exome AF: 0.242

GnomAD4 genome AF: 0.215 AC: 32738 AN: 152116 Hom.: 3990 Cov.: 31 AF XY: 0.211 AC XY: 15694 AN XY: 74362

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.232

Gnomad4 EAS AF: 0.184

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.283

Gnomad4 OTH AF: 0.224

Alfa AF: 0.264 Hom.: 5000

Bravo AF: 0.214

Asia WGS AF: 0.155 AC: 539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.0
DANN	Benign	0.60

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

LitVar

Other links and lift over

dbSNP: rs11544374; hg19: chr11-57004577; COSMIC: COSV57242922;