rs11544374

Variant names:

• chr11-57237103-C-T
• rs11544374
• NM_005161.6:c.-99G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 23 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: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005161.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APLNR	NM_005161.6	MANE Select	c.-99G>A		5_prime_UTR	Exon 1 of 1	NP_005152.1
	APLNR	NR_027991.2		n.148G>A		non_coding_transcript_exon	Exon 1 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APLNR	ENST00000606794.2	TSL:6 MANE Select	c.-99G>A		5_prime_UTR	Exon 1 of 1	ENSP00000475344.1
	APLNR	ENST00000257254.3	TSL:1	n.-99G>A		non_coding_transcript_exon	Exon 1 of 2	ENSP00000257254.3
	APLNR	ENST00000257254.3	TSL:1	n.-99G>A		5_prime_UTR	Exon 1 of 2	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

African (AFR) AF: 0.0937 AC: 2426 AN: 25888

American (AMR) AF: 0.242 AC: 5999 AN: 24830

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 4403 AN: 18428

East Asian (EAS) AF: 0.225 AC: 8236 AN: 36592

South Asian (SAS) AF: 0.215 AC: 13542 AN: 63086

European-Finnish (FIN) AF: 0.215 AC: 10229 AN: 47634

Middle Eastern (MID) AF: 0.240 AC: 809 AN: 3376

European-Non Finnish (NFE) AF: 0.280 AC: 248744 AN: 889240

Other (OTH) AF: 0.242 AC: 11863 AN: 49064

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

African (AFR) AF: 0.107 AC: 4457 AN: 41518

American (AMR) AF: 0.220 AC: 3356 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 804 AN: 3470

East Asian (EAS) AF: 0.184 AC: 949 AN: 5144

South Asian (SAS) AF: 0.197 AC: 950 AN: 4818

European-Finnish (FIN) AF: 0.204 AC: 2160 AN: 10600

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.283 AC: 19251 AN: 67974

Other (OTH) AF: 0.224 AC: 473 AN: 2112

Alfa AF: 0.258 Hom.: 6011

Bravo AF: 0.214

Asia WGS AF: 0.155 AC: 539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.0
DANN	Benign	0.60
PhyloP100		1.4
PromoterAI		0.043	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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