7-101163359-A-G

Variant names:

• chr7-101163359-A-G
• rs1474255877
• NM_003378.4:c.1485T>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_003378.4(VGF):​c.1485T>C​(p.Arg495Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000797 in 501,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R495R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 11)
  • Exomes 𝑓: 0.0000080 (0 hom.)
• Consequence: VGF NM_003378.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.512
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP7: Synonymous conserved (PhyloP=-0.512 with no splicing effect.

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.1485T>C	p.Arg495Arg	synonymous	Exon 2 of 2	NP_003369.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VGF	ENST00000249330.3	TSL:1 MANE Select	c.1485T>C	p.Arg495Arg	synonymous	Exon 2 of 2	ENSP00000249330.2	O15240
	VGF	ENST00000445482.2	TSL:5	c.1485T>C	p.Arg495Arg	synonymous	Exon 2 of 2	ENSP00000400884.2	O15240
	VGF	ENST00000970416.1		c.1485T>C	p.Arg495Arg	synonymous	Exon 2 of 2	ENSP00000640475.1

Frequencies

GnomAD3 genomes Cov.: 11

GnomAD2 exomes AF: 0.00000790 AC: 1 AN: 126574 AF XY: 0.0000145

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: 0.00000797 AC: 4 AN: 501890 Hom.: 0 Cov.: 23 AF XY: 0.0000116 AC XY: 3 AN XY: 257542

African (AFR) AF: 0.00 AC: 0 AN: 13038

American (AMR) AF: 0.00 AC: 0 AN: 28472

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10632

East Asian (EAS) AF: 0.00 AC: 0 AN: 10864

South Asian (SAS) AF: 0.0000526 AC: 3 AN: 56988

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10818

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1404

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 349744

Other (OTH) AF: 0.0000502 AC: 1 AN: 19930

GnomAD4 genome Cov.: 11

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.9
DANN	Benign	0.58
PhyloP100		-0.51

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

Other links and lift over

dbSNP: rs1474255877; hg19: chr7-100806640;