rs10520258

Variant names:

• chr4-173391598-G-A
• rs10520258
• NM_007281.4:c.-14-170C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007281.4(SCRG1):​c.-14-170C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0333 in 152,232 control chromosomes in the GnomAD database, including 171 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 0.033 (171 hom., cov: 32)
• Consequence: SCRG1 NM_007281.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.851

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCRG1	NM_007281.4	c.-14-170C>T		intron_variant	Intron 1 of 2	ENST00000296506.8	NP_009212.1
SCRG1	NM_001329597.2	c.-14-170C>T		intron_variant	Intron 2 of 3		NP_001316526.1
SCRG1	XM_047449563.1	c.-14-170C>T		intron_variant	Intron 2 of 3		XP_047305519.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCRG1	ENST00000296506.8	c.-14-170C>T		intron_variant	Intron 1 of 2	1	NM_007281.4	ENSP00000296506.2
SCRG1	ENST00000512188.1	n.-14-170C>T		intron_variant	Intron 6 of 8	2		ENSP00000425404.1

Frequencies

GnomAD3 genomes AF: 0.0333 AC: 5069 AN: 152114 Hom.: 171 Cov.: 32

Gnomad AFR AF: 0.0898

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0189

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00373

Gnomad FIN AF: 0.0130

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0115

Gnomad OTH AF: 0.0273

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

GnomAD4 genome AF: 0.0333 AC: 5074 AN: 152232 Hom.: 171 Cov.: 32 AF XY: 0.0327 AC XY: 2436 AN XY: 74442

Gnomad4 AFR AF: 0.0896

Gnomad4 AMR AF: 0.0189

Gnomad4 ASJ AF: 0.0153

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00394

Gnomad4 FIN AF: 0.0130

Gnomad4 NFE AF: 0.0115

Gnomad4 OTH AF: 0.0270

Alfa AF: 0.0229 Hom.: 11

Bravo AF: 0.0365

Asia WGS AF: 0.00722 AC: 25 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.14
DANN	Benign	0.71

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: rs10520258; hg19: chr4-174312749;