rs12490383

Variant names:

• chr3-47452667-T-C
• rs12490383
• NM_012235.4:c.-98-9576A>G

Variant summary

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

The NM_012235.4(SCAP):​c.-98-9576A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,176 control chromosomes in the GnomAD database, including 2,539 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 0.15 (2539 hom., cov: 32)
• Consequence: SCAP NM_012235.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.564
• Publications: 9 publications found

Genes affected

SCAP (HGNC:30634): (SREBF chaperone) This gene encodes a protein with a sterol sensing domain (SSD) and seven WD domains. In the presence of cholesterol, this protein binds to sterol regulatory element binding proteins (SREBPs) and mediates their transport from the ER to the Golgi. The SREBPs are then proteolytically cleaved and regulate sterol biosynthesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCAP	NM_012235.4	c.-98-9576A>G		intron_variant	Intron 1 of 22	ENST00000265565.10	NP_036367.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCAP	ENST00000265565.10	c.-98-9576A>G		intron_variant	Intron 1 of 22	1	NM_012235.4	ENSP00000265565.5

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22486 AN: 152058 Hom.: 2540 Cov.: 32

Gnomad AFR AF: 0.0368

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.168

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

GnomAD4 genome AF: 0.148 AC: 22495 AN: 152176 Hom.: 2539 Cov.: 32 AF XY: 0.157 AC XY: 11646 AN XY: 74374

African (AFR) AF: 0.0367 AC: 1524 AN: 41548

American (AMR) AF: 0.280 AC: 4270 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 615 AN: 3466

East Asian (EAS) AF: 0.485 AC: 2505 AN: 5170

South Asian (SAS) AF: 0.304 AC: 1468 AN: 4822

European-Finnish (FIN) AF: 0.130 AC: 1382 AN: 10594

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10097 AN: 67996

Other (OTH) AF: 0.169 AC: 356 AN: 2108

Alfa AF: 0.159 Hom.: 2730

Bravo AF: 0.155

Asia WGS AF: 0.331 AC: 1146 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	4.8
DANN	Benign	0.80
PhyloP100		-0.56
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: rs12490383; hg19: chr3-47494157;