Genetic Variant APLNR:n.-99G>A (chr11-57237103-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000257254.3(APLNR):n.-99G>A 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 0.259 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
ENST00000257254.3 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.42

Publications

23 publications found

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APLNR	NM_005161.6 link	c.-99G>A		5_prime_UTR_variant	Exon 1 of 1	ENST00000606794.2	NP_005152.1	P35414B2RDH3B3KQN4
APLNR	NR_027991.2 link	n.148G>A		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
APLNR	ENST00000257254.3 link	n.-99G>A	non_coding_transcript_exon_variant	Exon 1 of 2	1		ENSP00000257254.3	P35414
APLNR	ENST00000606794.2 link	c.-99G>A	5_prime_UTR_variant	Exon 1 of 1	6	NM_005161.6	ENSP00000475344.1	P35414
APLNR	ENST00000257254.3 link	n.-99G>A	5_prime_UTR_variant	Exon 1 of 2	1		ENSP00000257254.3	P35414

Frequencies

GnomAD3 genomes

AF:

0.215

AC:

32741

AN:

151996

Hom.:

3995

Cov.:

show subpopulations

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.:

AF XY:

0.263

AC XY:

150499

AN XY:

572930

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

11127

22254

33382

44509

55636

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8020

16040

24060

32080

40100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.215

AC:

32738

AN:

152116

Hom.:

3990

Cov.:

AF XY:

0.211

AC XY:

15694

AN XY:

74362

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.283

AC:

19251

AN:

67974

Other (OTH)

AF:

0.224

AC:

473

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1260

2521

3781

5042

6302

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

352

704

1056

1408

1760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

8.0

(source)

DANN

Benign

0.60

PhyloP100

1.4

PromoterAI

0.043

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over