rs133290

Positions:

• chr22-41871601-C-A
• chr22-41871601-C-G

Variant summary

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

The NM_004599.4(SREBF2):​c.867+566C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.606 in 151,998 control chromosomes in the GnomAD database, including 29,567 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 0.61 (29567 hom., cov: 32)
• Consequence: SREBF2 NM_004599.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.220

Genes affected

SREBF2 (HGNC:11290): (sterol regulatory element binding transcription factor 2) This gene encodes a member of the a ubiquitously expressed transcription factor that controls cholesterol homeostasis by regulating transcription of sterol-regulated genes. The encoded protein contains a basic helix-loop-helix-leucine zipper (bHLH-Zip) domain and binds the sterol regulatory element 1 motif. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SREBF2	NM_004599.4	c.867+566C>A		intron_variant		ENST00000361204.9	NP_004590.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SREBF2	ENST00000361204.9	c.867+566C>A		intron_variant		1	NM_004599.4	ENSP00000354476	P3
SREBF2	ENST00000424354.5	c.867+566C>A		intron_variant, NMD_transcript_variant		1		ENSP00000395728
SREBF2	ENST00000710853.1	c.777+566C>A		intron_variant				ENSP00000518526	A2

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91940 AN: 151880 Hom.: 29517 Cov.: 32

Gnomad AFR AF: 0.810

Gnomad AMI AF: 0.483

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.574

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

GnomAD4 genome AF: 0.606 AC: 92042 AN: 151998 Hom.: 29567 Cov.: 32 AF XY: 0.602 AC XY: 44747 AN XY: 74310

Gnomad4 AFR AF: 0.810

Gnomad4 AMR AF: 0.669

Gnomad4 ASJ AF: 0.614

Gnomad4 EAS AF: 0.715

Gnomad4 SAS AF: 0.551

Gnomad4 FIN AF: 0.428

Gnomad4 NFE AF: 0.492

Gnomad4 OTH AF: 0.568

Alfa AF: 0.537 Hom.: 11309

Bravo AF: 0.637

Asia WGS AF: 0.598 AC: 2081 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.8
DANN	Benign	0.37

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: rs133290; hg19: chr22-42267605;