rs6494587

Variant names:

• chr15-32689442-G-A
• rs6494587
• NM_001144757.3:c.490-2268G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-32689442-G-A
• chr15-32689442-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001144757.3(SCG5):​c.490-2268G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 151,942 control chromosomes in the GnomAD database, including 1,797 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (1797 hom., cov: 32)
• Consequence: SCG5 NM_001144757.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.89
• Publications: 8 publications found

Genes affected

SCG5 (HGNC:10816): (secretogranin V) This gene encodes a secreted chaperone protein that prevents the aggregation of other secreted proteins, including proteins that are associated with neurodegenerative and metabolic disease. The encoded protein may be best known for its role in the trafficking and activation of prohormone convertase PC2 (encoded by Gene ID: 5126). Phosphorylation of the encoded protein has been shown to have an inhibitory effect on its chaperone function. This gene also produces a ARHGAP11A-SCG5 readthrough transcript and ARHGAP11A-SCG5 protein. [provided by RefSeq, Feb 2019]

ARHGAP11A-SCG5 (HGNC:56310): (ARHGAP11A-SCG5 readthrough) This locus represents naturally occurring readthrough transcription between the neighboring ARHGAP11A (Rho GTPase activating protein 11A) and SCG5 (secretogranin V) genes on chromosome 15q13.3. The readthrough transcript encodes a fusion protein that shares sequence identity with both the ARHGAP11A and SCG5 gene products. [provided by RefSeq, Feb 2019]

ENSG00000298771 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCG5	NM_001144757.3	c.490-2268G>A		intron_variant	Intron 4 of 5	ENST00000300175.9	NP_001138229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCG5	ENST00000300175.9	c.490-2268G>A		intron_variant	Intron 4 of 5	1	NM_001144757.3	ENSP00000300175.4
ARHGAP11A-SCG5	ENST00000692248.1	c.1729-2268G>A		intron_variant	Intron 12 of 13			ENSP00000510771.1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19955 AN: 151822 Hom.: 1794 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.0857

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.0803

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0739

Gnomad OTH AF: 0.129

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.131 AC: 19973 AN: 151942 Hom.: 1797 Cov.: 32 AF XY: 0.138 AC XY: 10258 AN XY: 74242

African (AFR) AF: 0.184 AC: 7620 AN: 41396

American (AMR) AF: 0.119 AC: 1811 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0803 AC: 278 AN: 3464

East Asian (EAS) AF: 0.440 AC: 2269 AN: 5152

South Asian (SAS) AF: 0.233 AC: 1119 AN: 4812

European-Finnish (FIN) AF: 0.140 AC: 1477 AN: 10550

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0739 AC: 5023 AN: 67980

Other (OTH) AF: 0.130 AC: 274 AN: 2112

Alfa AF: 0.0929 Hom.: 2785

Bravo AF: 0.131

Asia WGS AF: 0.320 AC: 1108 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	12
DANN	Benign	0.52
PhyloP100		2.9
Mutation Taster		=100/0	polymorphism (auto)

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: rs6494587; hg19: chr15-32981643;