chr4-173450630-C-T

Variant names:

• chr4-173450630-C-T
• rs11132986
• NM_001329597.2:c.-15+15274G>A

Variant summary

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

The NM_001329597.2(SCRG1):​c.-15+15274G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 152,020 control chromosomes in the GnomAD database, including 6,778 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 0.29 (6778 hom., cov: 32)
• Consequence: SCRG1 NM_001329597.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.640
• Publications: 4 publications found

Genes affected

SCRG1 (HGNC:17036): (stimulator of chondrogenesis 1) Scrapie-responsive gene 1 is associated with neurodegenerative changes observed in transmissible spongiform encephalopathies. It may play a role in host response to prion-associated infections. The scrapie responsive protein 1 may be partly included in the membrane or secreted by the cells due to its hydrophobic N-terminus. In addition, the encoded protein can interact with bone marrow stromal cell antigen 1 (BST1) to enhance the differentiation potentials of human mesenchymal stem cells during tissue and bone regeneration. [provided by RefSeq, Jul 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCRG1	NM_001329597.2	c.-15+15274G>A		intron_variant	Intron 2 of 3		NP_001316526.1
SCRG1	XM_047449563.1	c.-15+15274G>A		intron_variant	Intron 2 of 3		XP_047305519.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43913 AN: 151902 Hom.: 6760 Cov.: 32

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.314

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

GnomAD4 genome AF: 0.289 AC: 43975 AN: 152020 Hom.: 6778 Cov.: 32 AF XY: 0.295 AC XY: 21894 AN XY: 74278

African (AFR) AF: 0.355 AC: 14741 AN: 41478

American (AMR) AF: 0.346 AC: 5279 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 930 AN: 3468

East Asian (EAS) AF: 0.283 AC: 1460 AN: 5156

South Asian (SAS) AF: 0.467 AC: 2241 AN: 4798

European-Finnish (FIN) AF: 0.242 AC: 2552 AN: 10556

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.232 AC: 15797 AN: 67984

Other (OTH) AF: 0.316 AC: 669 AN: 2114

Alfa AF: 0.240 Hom.: 2481

Bravo AF: 0.300

Asia WGS AF: 0.388 AC: 1347 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.6
DANN	Benign	0.57
PhyloP100		0.64

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11132986; hg19: chr4-174371781;