rs7177843

Variant names:

• chr15-32679733-C-T
• rs7177843
• NM_001144757.3:c.227-33C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-32679733-C-T
• chr15-32679733-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001144757.3(SCG5):​c.227-33C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 1,606,720 control chromosomes in the GnomAD database, including 56,014 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (5554 hom., cov: 32)
  • Exomes 𝑓: 0.25 (50460 hom.)
• Consequence: SCG5 NM_001144757.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0700
• Publications: 11 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 15-32679733-C-T is Benign according to our data. Variant chr15-32679733-C-T is described in ClinVar as Benign. ClinVar VariationId is 1239157.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.575 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCG5	NM_001144757.3	MANE Select	c.227-33C>T		intron	N/A	NP_001138229.1	P05408-1
	ARHGAP11A-SCG5	NM_001368319.1		c.1469-33C>T		intron	N/A	NP_001355248.1	A0A8I5KWH8
	SCG5	NM_003020.5		c.227-33C>T		intron	N/A	NP_003011.1	P05408-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCG5	ENST00000300175.9	TSL:1 MANE Select	c.227-33C>T		intron	N/A	ENSP00000300175.4	P05408-1
	ARHGAP11A-SCG5	ENST00000692248.1		c.1469-33C>T		intron	N/A	ENSP00000510771.1	A0A8I5KWH8
	SCG5	ENST00000413748.6	TSL:1	c.227-33C>T		intron	N/A	ENSP00000388560.2	P05408-2

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39083 AN: 151948 Hom.: 5552 Cov.: 32

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.592

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.260

GnomAD2 exomes AF: 0.299 AC: 74352 AN: 248296 AF XY: 0.301

Gnomad AFR exome AF: 0.217

Gnomad AMR exome AF: 0.317

Gnomad ASJ exome AF: 0.194

Gnomad EAS exome AF: 0.587

Gnomad FIN exome AF: 0.371

Gnomad NFE exome AF: 0.226

Gnomad OTH exome AF: 0.280

GnomAD4 exome AF: 0.249 AC: 362631 AN: 1454654 Hom.: 50460 Cov.: 31 AF XY: 0.254 AC XY: 183623 AN XY: 723890

African (AFR) AF: 0.214 AC: 7131 AN: 33374

American (AMR) AF: 0.312 AC: 13944 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 4980 AN: 26048

East Asian (EAS) AF: 0.589 AC: 23360 AN: 39646

South Asian (SAS) AF: 0.403 AC: 34667 AN: 85976

European-Finnish (FIN) AF: 0.369 AC: 19683 AN: 53374

Middle Eastern (MID) AF: 0.271 AC: 1564 AN: 5764

European-Non Finnish (NFE) AF: 0.218 AC: 241265 AN: 1105686

Other (OTH) AF: 0.267 AC: 16037 AN: 60114

GnomAD4 genome AF: 0.257 AC: 39102 AN: 152066 Hom.: 5554 Cov.: 32 AF XY: 0.269 AC XY: 19990 AN XY: 74326

African (AFR) AF: 0.219 AC: 9072 AN: 41488

American (AMR) AF: 0.282 AC: 4303 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 655 AN: 3470

East Asian (EAS) AF: 0.592 AC: 3061 AN: 5170

South Asian (SAS) AF: 0.421 AC: 2030 AN: 4818

European-Finnish (FIN) AF: 0.366 AC: 3865 AN: 10554

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.225 AC: 15302 AN: 67978

Other (OTH) AF: 0.260 AC: 549 AN: 2108

Alfa AF: 0.233 Hom.: 16874

Bravo AF: 0.245

Asia WGS AF: 0.486 AC: 1687 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.3
DANN	Benign	0.73
PhyloP100		0.070
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: rs7177843; hg19: chr15-32971934; COSMIC: COSV107356599; COSMIC: COSV107356599;