4-164877355-T-C

Position:

• chr4-164877355-T-C

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001297550.2(APELA):​c.24T>C​(p.Phe8Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00221 in 399,060 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0044 (5 hom., cov: 33)
  • Exomes 𝑓: 0.00083 (0 hom.)
• Consequence: APELA NM_001297550.2 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.34

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 4-164877355-T-C is Benign according to our data. Variant chr4-164877355-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 718276.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.34 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APELA	NM_001297550.2	c.24T>C	p.Phe8Phe	synonymous_variant	1/3	ENST00000507152.6	NP_001284479.1
APELA	XM_017007623.2	c.24T>C	p.Phe8Phe	synonymous_variant	1/3		XP_016863112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APELA	ENST00000507152.6	c.24T>C	p.Phe8Phe	synonymous_variant	1/3	1	NM_001297550.2	ENSP00000484618.1
APELA	ENST00000515275.1	c.24T>C	p.Phe8Phe	synonymous_variant	1/2	3		ENSP00000480045.1
APELA	ENST00000510062.5	n.24T>C		non_coding_transcript_exon_variant	1/4	3		ENSP00000478306.1

Frequencies

GnomAD3 genomes AF: 0.00443 AC: 674 AN: 152234 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.0148

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00236

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.00239

GnomAD4 exome AF: 0.000835 AC: 206 AN: 246708 Hom.: 0 Cov.: 0 AF XY: 0.000688 AC XY: 86 AN XY: 125044

Gnomad4 AFR exome AF: 0.0130

Gnomad4 AMR exome AF: 0.00215

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000330

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000348

Gnomad4 OTH exome AF: 0.00220

GnomAD4 genome AF: 0.00444 AC: 677 AN: 152352 Hom.: 5 Cov.: 33 AF XY: 0.00405 AC XY: 302 AN XY: 74502

Gnomad4 AFR AF: 0.0148

Gnomad4 AMR AF: 0.00235

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.00236

Alfa AF: 0.00305 Hom.: 0

Bravo AF: 0.00467

Asia WGS AF: 0.000866 AC: 3 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	Jun 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.0
DANN	Benign	0.48

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: rs150754288; hg19: chr4-165798507;