Genetic Variant NM_003378.4:c.1507G>A (chr7-101163337-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_003378.4(VGF):c.1507G>A(p.Val503Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V503A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00055 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

VGF
NM_003378.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.598

Publications

0 publications found

Variant links:

Genes affected

VGF (HGNC:12684): (VGF nerve growth factor inducible) This gene is specifically expressed in a subpopulation of neuroendocrine cells, and is upregulated by nerve growth factor. The structural organization of this gene is similar to that of the rat gene, and both the translated and the untranslated regions show a high degree of sequence similarity to the rat gene. The encoded secretory protein also shares similarities with the secretogranin/chromogranin family, however, its exact function is not known. [provided by RefSeq, Jul 2008]

VGF links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.050408095).

BS2

High AC in GnomAd4 at 6 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003378.4. 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
	VGF	NM_003378.4	MANE Select	c.1507G>A	p.Val503Ile	missense	Exon 2 of 2	NP_003369.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VGF	ENST00000249330.3	TSL:1 MANE Select	c.1507G>A	p.Val503Ile	missense	Exon 2 of 2	ENSP00000249330.2	O15240
VGF	ENST00000445482.2	TSL:5	c.1507G>A	p.Val503Ile	missense	Exon 2 of 2	ENSP00000400884.2	O15240
VGF	ENST00000970416.1		c.1507G>A	p.Val503Ile	missense	Exon 2 of 2	ENSP00000640475.1

Frequencies

GnomAD3 genomes

AF:

0.000554

AC:

AN:

10828

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000792

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00138

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000334

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000128

AC:

AN:

78386

AF XY:

0.0000243

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000336

AC:

AN:

237800

Hom.:

Cov.:

AF XY:

0.0000402

AC XY:

AN XY:

124292

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

7590

American (AMR)

AF:

0.00

AC:

AN:

21958

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

6178

East Asian (EAS)

AF:

0.00

AC:

AN:

6956

South Asian (SAS)

AF:

0.0000295

AC:

AN:

33882

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5720

Middle Eastern (MID)

AF:

0.00

AC:

AN:

744

European-Non Finnish (NFE)

AF:

0.0000484

AC:

AN:

144720

Other (OTH)

AF:

0.00

AC:

AN:

10052

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.000554

AC:

AN:

10832

Hom.:

Cov.:

AF XY:

0.000375

AC XY:

AN XY:

5332

show subpopulations

African (AFR)

AF:

0.000791

AC:

AN:

2528

American (AMR)

AF:

0.00138

AC:

AN:

724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

300

East Asian (EAS)

AF:

0.00

AC:

AN:

358

South Asian (SAS)

AF:

0.00248

AC:

AN:

404

European-Finnish (FIN)

AF:

0.00

AC:

AN:

302

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.000334

AC:

AN:

5982

Other (OTH)

AF:

0.00

AC:

AN:

130

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.600

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.092

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.44

M_CAP

Pathogenic

0.57

MetaRNN

Benign

0.050

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-0.60

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

0.030

REVEL

Benign

0.10

Sift

Benign

0.23

Sift4G

Benign

0.30

Polyphen

0.0030

Vest4

0.089

MutPred

0.081

Loss of methylation at R504 (P = 0.1041)

MVP

0.043

MPC

0.54

ClinPred

0.074

GERP RS

1.3

Varity_R

0.088

gMVP

0.050

Mutation Taster

=99/1

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