rs11711824

Variant names:

• chr3-47426771-C-T
• rs11711824
• NM_012235.4:c.737+386G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012235.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCAP	NM_012235.4	MANE Select	c.737+386G>A		intron	N/A	NP_036367.2
	SCAP	NM_001320044.2		c.-28-602G>A		intron	N/A	NP_001306973.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCAP	ENST00000265565.10	TSL:1 MANE Select	c.737+386G>A		intron	N/A	ENSP00000265565.5
	SCAP	ENST00000648151.1		c.737+386G>A		intron	N/A	ENSP00000497087.1
	SCAP	ENST00000320017.10	TSL:2	n.253-2726G>A		intron	N/A	ENSP00000324296.6

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

African (AFR) AF: 0.282 AC: 11695 AN: 41472

American (AMR) AF: 0.494 AC: 7558 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1841 AN: 3470

East Asian (EAS) AF: 0.473 AC: 2437 AN: 5156

South Asian (SAS) AF: 0.532 AC: 2569 AN: 4828

European-Finnish (FIN) AF: 0.628 AC: 6639 AN: 10570

Middle Eastern (MID) AF: 0.483 AC: 141 AN: 292

European-Non Finnish (NFE) AF: 0.603 AC: 41006 AN: 67968

Other (OTH) AF: 0.501 AC: 1057 AN: 2110

Alfa AF: 0.556 Hom.: 29586

Bravo AF: 0.474

Asia WGS AF: 0.538 AC: 1870 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.078
DANN	Benign	0.33
PhyloP100		-1.5
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: rs11711824; hg19: chr3-47468261;