4-164879002-T-C

Position:

• chr4-164879002-T-C

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The ENST00000507152.6(APELA):​c.159T>C​(p.Phe53=) 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 ENST00000507152.6 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.953

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

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APELA	NM_001297550.2	c.159T>C	p.Phe53=	synonymous_variant	2/3	ENST00000507152.6	NP_001284479.1
APELA	XM_017007623.2	c.159T>C	p.Phe53=	synonymous_variant	2/3		XP_016863112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APELA	ENST00000507152.6	c.159T>C	p.Phe53=	synonymous_variant	2/3	1	NM_001297550.2	ENSP00000484618	P1
APELA	ENST00000515275.1	c.159T>C	p.Phe53=	synonymous_variant	2/2	3		ENSP00000480045	P1
APELA	ENST00000510062.5	c.159T>C	p.Phe53=	synonymous_variant, NMD_transcript_variant	2/4	3		ENSP00000478306

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

Gnomad4 AFR exome AF: 0.657

Gnomad4 AMR exome AF: 0.497

Gnomad4 ASJ exome AF: 0.623

Gnomad4 EAS exome AF: 0.501

Gnomad4 SAS exome AF: 0.619

Gnomad4 FIN exome AF: 0.496

Gnomad4 NFE exome AF: 0.579

Gnomad4 OTH exome AF: 0.568

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

Gnomad4 AFR AF: 0.655

Gnomad4 AMR AF: 0.516

Gnomad4 ASJ AF: 0.625

Gnomad4 EAS AF: 0.508

Gnomad4 SAS AF: 0.618

Gnomad4 FIN AF: 0.484

Gnomad4 NFE AF: 0.579

Gnomad4 OTH AF: 0.574

Alfa AF: 0.582 Hom.: 42852

Bravo AF: 0.591

Asia WGS AF: 0.557 AC: 1936 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

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

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: rs4541465; hg19: chr4-165800154;