rs6494587

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
SCG5	NM_001144757.3	c.490-2268G>A		intron_variant		ENST00000300175.9
ARHGAP11A-SCG5	NM_001368319.1	c.1729-2268G>A		intron_variant
LOC105370756	XR_932083.3	n.69+753C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCG5	ENST00000300175.9	c.490-2268G>A		intron_variant		1	NM_001144757.3	P1

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

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.0803

Gnomad4 EAS AF: 0.440

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.0739

Gnomad4 OTH AF: 0.130

Alfa AF: 0.0870 Hom.: 1579

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

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

Other links and lift over

dbSNP: rs6494587; hg19: chr15-32981643;