rs4541465

Variant names:

• chr4-164879002-T-C
• rs4541465
• NM_001297550.2:c.159T>C

Your query was ambiguous. Multiple possible variants found:

• chr4-164879002-T-C
• chr4-164879002-T-A
• chr4-164879002-T-G

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001297550.2(APELA):​c.159T>C​(p.Phe53Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 398,648 control chromosomes in the GnomAD database, including 66,306 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (26418 hom., cov: 32)
  • Exomes 𝑓: 0.57 (39888 hom.)
• Consequence: APELA NM_001297550.2 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.953
• Publications: 5 publications found

Genes affected

APELA (HGNC:48925): (apelin receptor early endogenous ligand) This gene encodes a peptide hormone that binds to the Apelin receptor. The encoded protein is required for heart development in zebrafish and has been shown to maintain self-renewal of human embryonic stem cells through activation of the PI3K/AKT pathway. Experiments in human and mouse cell lines point to additional roles for the encoded protein in angiogenesis and regulation of vascular tone. [provided by RefSeq, Jul 2016]

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 4-164879002-T-C is Benign according to our data. Variant chr4-164879002-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 769296.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.953 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001297550.2. 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
	APELA	NM_001297550.2	MANE Select	c.159T>C	p.Phe53Phe	synonymous	Exon 2 of 3	NP_001284479.1	P0DMC3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APELA	ENST00000507152.6	TSL:1 MANE Select	c.159T>C	p.Phe53Phe	synonymous	Exon 2 of 3	ENSP00000484618.1	P0DMC3
	APELA	ENST00000515275.1	TSL:3	c.159T>C	p.Phe53Phe	synonymous	Exon 2 of 2	ENSP00000480045.1	P0DMC3
	APELA	ENST00000914507.1		c.159T>C	p.Phe53Phe	synonymous	Exon 2 of 3	ENSP00000584566.1

Frequencies

GnomAD3 genomes AF: 0.586 AC: 89054 AN: 151900 Hom.: 26384 Cov.: 32

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.550

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.625

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.573

GnomAD4 exome AF: 0.566 AC: 139558 AN: 246630 Hom.: 39888 Cov.: 0 AF XY: 0.568 AC XY: 70945 AN XY: 125002

African (AFR) AF: 0.657 AC: 4718 AN: 7182

American (AMR) AF: 0.497 AC: 3694 AN: 7434

Ashkenazi Jewish (ASJ) AF: 0.623 AC: 5751 AN: 9234

East Asian (EAS) AF: 0.501 AC: 11461 AN: 22868

South Asian (SAS) AF: 0.619 AC: 1876 AN: 3030

European-Finnish (FIN) AF: 0.496 AC: 10537 AN: 21252

Middle Eastern (MID) AF: 0.566 AC: 732 AN: 1294

European-Non Finnish (NFE) AF: 0.579 AC: 91495 AN: 157976

Other (OTH) AF: 0.568 AC: 9294 AN: 16360

GnomAD4 genome AF: 0.586 AC: 89142 AN: 152018 Hom.: 26418 Cov.: 32 AF XY: 0.580 AC XY: 43122 AN XY: 74292

African (AFR) AF: 0.655 AC: 27167 AN: 41454

American (AMR) AF: 0.516 AC: 7875 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.625 AC: 2169 AN: 3472

East Asian (EAS) AF: 0.508 AC: 2622 AN: 5162

South Asian (SAS) AF: 0.618 AC: 2986 AN: 4828

European-Finnish (FIN) AF: 0.484 AC: 5104 AN: 10554

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.579 AC: 39352 AN: 67966

Other (OTH) AF: 0.574 AC: 1213 AN: 2114

Alfa AF: 0.588 Hom.: 99998

Bravo AF: 0.591

Asia WGS AF: 0.557 AC: 1936 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	8.8
DANN	Benign	0.77
PhyloP100		0.95

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: rs4541465; hg19: chr4-165800154;