rs11635997

Variant names:

• chr15-32641892-G-A
• rs11635997
• NM_001144757.3:c.-8+114G>A

Variant summary

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

The NM_001368319.1(ARHGAP11A-SCG5):​c.1236-1694G>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: ARHGAP11A-SCG5 NM_001368319.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.625
• Publications: 12 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]

ENSG00000285948 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1229884.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001368319.1. 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.-8+114G>A		intron	N/A	NP_001138229.1
	ARHGAP11A-SCG5	NM_001368319.1		c.1236-1694G>A		intron	N/A	NP_001355248.1
	SCG5	NM_003020.5		c.-8+114G>A		intron	N/A	NP_003011.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCG5	ENST00000300175.9	TSL:1 MANE Select	c.-8+114G>A		intron	N/A	ENSP00000300175.4
	ARHGAP11A-SCG5	ENST00000692248.1		c.1236-1694G>A		intron	N/A	ENSP00000510771.1
	SCG5	ENST00000413748.6	TSL:1	c.-8+114G>A		intron	N/A	ENSP00000388560.2

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

African (AFR) AF: 0.00 AC: 0 AN: 6

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.611 AC: 11 AN: 18

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.480 AC: 24 AN: 50

Other (OTH) AF: 0.167 AC: 1 AN: 6

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

African (AFR) AF: 0.277 AC: 11475 AN: 41472

American (AMR) AF: 0.456 AC: 6974 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.638 AC: 2214 AN: 3470

East Asian (EAS) AF: 0.232 AC: 1199 AN: 5172

South Asian (SAS) AF: 0.533 AC: 2565 AN: 4808

European-Finnish (FIN) AF: 0.503 AC: 5309 AN: 10552

Middle Eastern (MID) AF: 0.534 AC: 156 AN: 292

European-Non Finnish (NFE) AF: 0.580 AC: 39433 AN: 67944

Other (OTH) AF: 0.514 AC: 1085 AN: 2112

Alfa AF: 0.555 Hom.: 51666

Bravo AF: 0.455

Asia WGS AF: 0.407 AC: 1417 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.74
CADD	Benign	14
DANN	Benign	0.86
PhyloP100		0.63
PromoterAI		0.017	Neutral
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: rs11635997; hg19: chr15-32934093;