rs7170561

Variant names:

• chr15-32676722-A-C
• rs7170561
• NM_001144757.3:c.227-3044A>C

Your query was ambiguous. Multiple possible variants found:

• chr15-32676722-A-C
• chr15-32676722-A-G

Variant summary

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

The NM_001144757.3(SCG5):​c.227-3044A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 152,090 control chromosomes in the GnomAD database, including 11,634 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 0.38 (11634 hom., cov: 33)
• Consequence: SCG5 NM_001144757.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0660
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001144757.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCG5	NM_001144757.3	MANE Select	c.227-3044A>C		intron	N/A	NP_001138229.1
	ARHGAP11A-SCG5	NM_001368319.1		c.1469-3044A>C		intron	N/A	NP_001355248.1
	SCG5	NM_003020.5		c.227-3044A>C		intron	N/A	NP_003011.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCG5	ENST00000300175.9	TSL:1 MANE Select	c.227-3044A>C		intron	N/A	ENSP00000300175.4
	ARHGAP11A-SCG5	ENST00000692248.1		c.1469-3044A>C		intron	N/A	ENSP00000510771.1
	SCG5	ENST00000413748.6	TSL:1	c.227-3044A>C		intron	N/A	ENSP00000388560.2

Frequencies

GnomAD3 genomes AF: 0.382 AC: 58053 AN: 151972 Hom.: 11614 Cov.: 33

Gnomad AFR AF: 0.444

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.380

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

GnomAD4 genome AF: 0.382 AC: 58118 AN: 152090 Hom.: 11634 Cov.: 33 AF XY: 0.388 AC XY: 28855 AN XY: 74358

African (AFR) AF: 0.444 AC: 18440 AN: 41488

American (AMR) AF: 0.381 AC: 5821 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1017 AN: 3472

East Asian (EAS) AF: 0.640 AC: 3315 AN: 5178

South Asian (SAS) AF: 0.467 AC: 2252 AN: 4822

European-Finnish (FIN) AF: 0.382 AC: 4037 AN: 10568

Middle Eastern (MID) AF: 0.411 AC: 120 AN: 292

European-Non Finnish (NFE) AF: 0.326 AC: 22122 AN: 67956

Other (OTH) AF: 0.379 AC: 801 AN: 2112

Alfa AF: 0.336 Hom.: 16627

Bravo AF: 0.381

Asia WGS AF: 0.540 AC: 1872 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.4
DANN	Benign	0.82
PhyloP100		0.066
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: rs7170561; hg19: chr15-32968923;