Genetic Variant NM_001297550.2:c.24T>C (chr4-164877355-T-C) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

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

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.34

Publications

0 publications found

Variant links:

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]

APELA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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

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.24T>C	p.Phe8Phe	synonymous	Exon 1 of 3	NP_001284479.1	P0DMC3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
APELA	ENST00000507152.6	TSL:1 MANE Select	c.24T>C	p.Phe8Phe	synonymous	Exon 1 of 3	ENSP00000484618.1	P0DMC3
APELA	ENST00000515275.1	TSL:3	c.24T>C	p.Phe8Phe	synonymous	Exon 1 of 2	ENSP00000480045.1	P0DMC3
APELA	ENST00000914507.1		c.24T>C	p.Phe8Phe	synonymous	Exon 1 of 3	ENSP00000584566.1

Frequencies

GnomAD3 genomes

AF:

0.00443

AC:

674

AN:

152234

Hom.:

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.000688

AC XY:

AN XY:

125044

show subpopulations

African (AFR)

AF:

0.0130

AC:

AN:

7180

American (AMR)

AF:

0.00215

AC:

AN:

7434

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9240

East Asian (EAS)

AF:

0.00

AC:

AN:

22888

South Asian (SAS)

AF:

0.000330

AC:

AN:

3032

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21250

Middle Eastern (MID)

AF:

0.00386

AC:

AN:

1294

European-Non Finnish (NFE)

AF:

0.000348

AC:

AN:

158016

Other (OTH)

AF:

0.00220

AC:

AN:

16374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00444

AC:

677

AN:

152352

Hom.:

Cov.:

AF XY:

0.00405

AC XY:

302

AN XY:

74502

show subpopulations

African (AFR)

AF:

0.0148

AC:

615

AN:

41582

American (AMR)

AF:

0.00235

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000265

AC:

AN:

68034

Other (OTH)

AF:

0.00236

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

113

150

188

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00402

Hom.:

Bravo

AF:

0.00467

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.0

(source)

DANN

Benign

0.48

PhyloP100

-1.3

PromoterAI

0.027

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over