rs11635997

chr15-32641892-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001144757.3(SCG5):c.-8+114G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 152,094 control chromosomes in the GnomAD database, including 18,185 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.47 (18175 hom., cov: 31)
  • Exomes 𝑓: 0.45 (10 hom.)
• Consequence: SCG5 NM_001144757.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.625

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 15-32641892-G-A is Benign according to our data. Variant chr15-32641892-G-A is described in ClinVar as [Benign]. Clinvar id is 1229884.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCG5	NM_001144757.3	c.-8+114G>A		intron_variant		ENST00000300175.9
ARHGAP11A-SCG5	NM_001368319.1	c.1236-1694G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCG5	ENST00000300175.9	c.-8+114G>A		intron_variant		1	NM_001144757.3	P1
SCG5	ENST00000413748.6	c.-8+114G>A		intron_variant		1
SCG5	ENST00000494364.5	c.-8+114G>A		intron_variant		5
SCG5	ENST00000497208.5	c.-8+114G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.467 AC: 70943 AN: 151894 Hom.: 18173 Cov.: 31

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.548

Gnomad NFE AF: 0.580

Gnomad OTH AF: 0.516

GnomAD4 exome AF: 0.450 AC: 36 AN: 80 Hom.: 10 AF XY: 0.446 AC XY: 25 AN XY: 56

Gnomad4 AFR exome AF: 0.00

Gnomad4 FIN exome AF: 0.611

Gnomad4 NFE exome AF: 0.480

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.467 AC: 70954 AN: 152014 Hom.: 18175 Cov.: 31 AF XY: 0.463 AC XY: 34425 AN XY: 74302

Gnomad4 AFR AF: 0.277

Gnomad4 AMR AF: 0.456

Gnomad4 ASJ AF: 0.638

Gnomad4 EAS AF: 0.232

Gnomad4 SAS AF: 0.533

Gnomad4 FIN AF: 0.503

Gnomad4 NFE AF: 0.580

Gnomad4 OTH AF: 0.514

Alfa AF: 0.571 Hom.: 36024

Bravo AF: 0.455

Asia WGS AF: 0.407 AC: 1417 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	14
Dann	Benign	0.86

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: rs11635997; hg19: chr15-32934093;