Variant 7-101163368-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_003378.4(VGF):c.1476G>C(p.Pro492=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0019 in 1,530,266 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0015 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 6 hom. )

Consequence

VGF
NM_003378.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.40

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 7-101163368-C-G is Benign according to our data. Variant chr7-101163368-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 712058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.4 with no splicing effect.

BS2

High AC in GnomAd4 at 212 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
VGF	NM_003378.4 linkuse as main transcript	c.1476G>C	p.Pro492=	synonymous_variant	2/2	ENST00000249330.3	NP_003369.2
VGF	XM_005250561.6 linkuse as main transcript	c.1476G>C	p.Pro492=	synonymous_variant	2/2		XP_005250618.1
VGF	XM_011516549.4 linkuse as main transcript	c.1476G>C	p.Pro492=	synonymous_variant	3/3		XP_011514851.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VGF	ENST00000249330.3 linkuse as main transcript	c.1476G>C	p.Pro492=	synonymous_variant	2/2	1	NM_003378.4	ENSP00000249330	P1
VGF	ENST00000445482.2 linkuse as main transcript	c.1476G>C	p.Pro492=	synonymous_variant	2/2	5		ENSP00000400884	P1

Frequencies

GnomAD3 genomes

AF:

0.00152

AC:

212

AN:

139126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000215

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00122

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000946

Gnomad FIN

AF:

0.00210

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00255

Gnomad OTH

AF:

0.000533

GnomAD3 exomes

AF:

0.00133

AC:

225

AN:

168940

Hom.:

AF XY:

0.00136

AC XY:

126

AN XY:

92820

show subpopulations

Gnomad AFR exome

AF:

0.000195

Gnomad AMR exome

AF:

0.00109

Gnomad ASJ exome

AF:

0.000510

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000919

Gnomad FIN exome

AF:

0.00183

Gnomad NFE exome

AF:

0.00200

Gnomad OTH exome

AF:

0.00218

GnomAD4 exome

AF:

0.00194

AC:

2699

AN:

1391066

Hom.:

Cov.:

AF XY:

0.00200

AC XY:

1371

AN XY:

686346

show subpopulations

Gnomad4 AFR exome

AF:

0.000186

Gnomad4 AMR exome

AF:

0.00116

Gnomad4 ASJ exome

AF:

0.000284

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000885

Gnomad4 FIN exome

AF:

0.00315

Gnomad4 NFE exome

AF:

0.00217

Gnomad4 OTH exome

AF:

0.00184

GnomAD4 genome

AF:

0.00152

AC:

212

AN:

139200

Hom.:

Cov.:

AF XY:

0.00152

AC XY:

103

AN XY:

67594

show subpopulations

Gnomad4 AFR

AF:

0.000215

Gnomad4 AMR

AF:

0.00122

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000947

Gnomad4 FIN

AF:

0.00210

Gnomad4 NFE

AF:

0.00255

Gnomad4 OTH

AF:

0.000527

Alfa

AF:

0.000858

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2022	VGF: BP4, BP7 -
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

-0.46

CADD

Benign

7.7

DANN

Benign

0.88

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over