rs11711824

Positions:

• chr3-47426771-C-T

Variant summary

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

The NM_012235.4(SCAP):​c.737+386G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 152,068 control chromosomes in the GnomAD database, including 20,289 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 0.50 (20289 hom., cov: 32)
• Consequence: SCAP NM_012235.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCAP	NM_012235.4	c.737+386G>A		intron_variant		ENST00000265565.10	NP_036367.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCAP	ENST00000265565.10	c.737+386G>A		intron_variant		1	NM_012235.4	ENSP00000265565	P1

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75308 AN: 151950 Hom.: 20281 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.603

Gnomad OTH AF: 0.498

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

GnomAD4 genome AF: 0.495 AC: 75342 AN: 152068 Hom.: 20289 Cov.: 32 AF XY: 0.494 AC XY: 36749 AN XY: 74340

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.494

Gnomad4 ASJ AF: 0.531

Gnomad4 EAS AF: 0.473

Gnomad4 SAS AF: 0.532

Gnomad4 FIN AF: 0.628

Gnomad4 NFE AF: 0.603

Gnomad4 OTH AF: 0.501

Alfa AF: 0.568 Hom.: 23609

Bravo AF: 0.474

Asia WGS AF: 0.538 AC: 1870 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.078
DANN	Benign	0.33

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: rs11711824; hg19: chr3-47468261;