rs77809319

Variant names:

• chr22-41900991-A-G
• rs77809319
• NM_004599.4:c.2907+493A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_004599.4(SREBF2):​c.2907+493A>G variant causes a intron change. The variant allele was found at a frequency of 0.000279 in 531,212 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00036 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00025 (0 hom.)
• Consequence: SREBF2 NM_004599.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.06
• Publications: 6 publications found

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]

MIR33A (HGNC:31634): (microRNA 33a) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004599.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SREBF2	NM_004599.4	MANE Select	c.2907+493A>G		intron	N/A	NP_004590.2
	MIR33A	NR_029507.1		n.48A>G		non_coding_transcript_exon	Exon 1 of 1
	SREBF2	NR_103834.2		n.3593+493A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SREBF2	ENST00000361204.9	TSL:1 MANE Select	c.2907+493A>G		intron	N/A	ENSP00000354476.4
	SREBF2	ENST00000424354.5	TSL:1	n.*1372+493A>G		intron	N/A	ENSP00000395728.1
	SREBF2	ENST00000491541.1	TSL:1	n.1878+493A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000362 AC: 55 AN: 152108 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00251

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000485

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000400 AC: 98 AN: 245238 AF XY: 0.000399

Gnomad AFR exome AF: 0.000192

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000910

Gnomad EAS exome AF: 0.00311

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000261

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000245 AC: 93 AN: 378986 Hom.: 0 Cov.: 0 AF XY: 0.000218 AC XY: 47 AN XY: 215784

African (AFR) AF: 0.0000953 AC: 1 AN: 10488

American (AMR) AF: 0.00 AC: 0 AN: 36050

Ashkenazi Jewish (ASJ) AF: 0.000943 AC: 11 AN: 11666

East Asian (EAS) AF: 0.00235 AC: 31 AN: 13166

South Asian (SAS) AF: 0.00 AC: 0 AN: 66070

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30708

Middle Eastern (MID) AF: 0.000351 AC: 1 AN: 2852

European-Non Finnish (NFE) AF: 0.000235 AC: 45 AN: 191330

Other (OTH) AF: 0.000240 AC: 4 AN: 16656

GnomAD4 genome AF: 0.000361 AC: 55 AN: 152226 Hom.: 0 Cov.: 32 AF XY: 0.000282 AC XY: 21 AN XY: 74420

African (AFR) AF: 0.000120 AC: 5 AN: 41554

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3466

East Asian (EAS) AF: 0.00252 AC: 13 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000485 AC: 33 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000219 Hom.: 0

Bravo AF: 0.000366

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	14
DANN	Benign	0.80
PhyloP100		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0

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: rs77809319; hg19: chr22-42296995;