4-173401980-C-A

Position:

• chr4-173401980-C-A

Variant summary

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

The NM_001329597.2(SCRG1):​c.-14-10552G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 152,062 control chromosomes in the GnomAD database, including 13,655 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 0.39 (13655 hom., cov: 32)
• Consequence: SCRG1 NM_001329597.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21

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]

ENSG00000288025 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCRG1	NM_001329597.2	c.-14-10552G>T		intron_variant			NP_001316526.1
SCRG1	XM_047449563.1	c.-14-10552G>T		intron_variant			XP_047305519.1
LOC112268474	XR_007058369.1	n.4639C>A		non_coding_transcript_exon_variant	1/2
LOC112268474	XR_002959832.2	n.115-738C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000288025	ENST00000664814.1	n.4211C>A		non_coding_transcript_exon_variant	1/3
SCRG1	ENST00000512188.1	n.-364+1144G>T		intron_variant		2		ENSP00000425404.1

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59242 AN: 151944 Hom.: 13660 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.555

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.535

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.509

Gnomad OTH AF: 0.411

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

GnomAD4 genome AF: 0.389 AC: 59224 AN: 152062 Hom.: 13655 Cov.: 32 AF XY: 0.390 AC XY: 28999 AN XY: 74326

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.358

Gnomad4 ASJ AF: 0.401

Gnomad4 EAS AF: 0.535

Gnomad4 SAS AF: 0.350

Gnomad4 FIN AF: 0.567

Gnomad4 NFE AF: 0.509

Gnomad4 OTH AF: 0.406

Alfa AF: 0.356 Hom.: 1643

Bravo AF: 0.366

Asia WGS AF: 0.400 AC: 1389 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.1
DANN	Benign	0.45

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17325472; hg19: chr4-174323131;