rs8037112

Variant names:

• chr15-32670558-A-G
• rs8037112
• NM_001144757.3:c.227-9208A>G

Your query was ambiguous. Multiple possible variants found:

• chr15-32670558-A-G
• chr15-32670558-A-T

Variant summary

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

The NM_001144757.3(SCG5):​c.227-9208A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 152,172 control chromosomes in the GnomAD database, including 32,100 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 0.65 (32100 hom., cov: 34)
• Consequence: SCG5 NM_001144757.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.645
• 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]

SCG5-AS1 (HGNC:40524): (SCG5 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCG5	NM_001144757.3	c.227-9208A>G		intron_variant	Intron 2 of 5	ENST00000300175.9	NP_001138229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCG5	ENST00000300175.9	c.227-9208A>G		intron_variant	Intron 2 of 5	1	NM_001144757.3	ENSP00000300175.4
ARHGAP11A-SCG5	ENST00000692248.1	c.1469-9208A>G		intron_variant	Intron 10 of 13			ENSP00000510771.1

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98411 AN: 152054 Hom.: 32034 Cov.: 34

Gnomad AFR AF: 0.716

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.624

Gnomad OTH AF: 0.618

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

GnomAD4 genome AF: 0.648 AC: 98543 AN: 152172 Hom.: 32100 Cov.: 34 AF XY: 0.644 AC XY: 47893 AN XY: 74406

African (AFR) AF: 0.717 AC: 29738 AN: 41504

American (AMR) AF: 0.669 AC: 10243 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.607 AC: 2103 AN: 3466

East Asian (EAS) AF: 0.511 AC: 2648 AN: 5182

South Asian (SAS) AF: 0.620 AC: 2990 AN: 4826

European-Finnish (FIN) AF: 0.607 AC: 6429 AN: 10588

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.624 AC: 42413 AN: 67986

Other (OTH) AF: 0.623 AC: 1316 AN: 2112

Alfa AF: 0.636 Hom.: 18493

Bravo AF: 0.657

Asia WGS AF: 0.597 AC: 2081 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.0
DANN	Benign	0.79
PhyloP100		-0.65
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: rs8037112; hg19: chr15-32962759;