rs8037112

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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:):

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

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
SCG5	NM_001144757.3	c.227-9208A>G		intron_variant		ENST00000300175.9	NP_001138229.1
ARHGAP11A-SCG5	NM_001368319.1	c.1469-9208A>G		intron_variant			NP_001355248.1
SCG5-AS1	NR_135505.1	n.77-1440T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCG5	ENST00000300175.9	c.227-9208A>G		intron_variant		1	NM_001144757.3	ENSP00000300175	P1

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

Gnomad4 AFR AF: 0.717

Gnomad4 AMR AF: 0.669

Gnomad4 ASJ AF: 0.607

Gnomad4 EAS AF: 0.511

Gnomad4 SAS AF: 0.620

Gnomad4 FIN AF: 0.607

Gnomad4 NFE AF: 0.624

Gnomad4 OTH AF: 0.623

Alfa AF: 0.637 Hom.: 16997

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

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: rs8037112; hg19: chr15-32962759;