22-41833088-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NR_157279.2(SREBF2-AS1):n.1116C>G variant causes a non coding transcript exon change. The variant allele was found at a frequency of 0.081 in 469,004 control chromosomes in the GnomAD database, including 1,947 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.070 (534 hom., cov: 31)
  • Exomes 𝑓: 0.086 (1413 hom.)
• Consequence: SREBF2-AS1 NR_157279.2 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.73

Genes affected

SREBF2-AS1 (HGNC:53953): (SREBF2 antisense RNA 1)

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=-0.22).
• BP6: Variant 22-41833088-G-C is Benign according to our data. Variant chr22-41833088-G-C is described in ClinVar as [Benign]. Clinvar id is 1262622.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.1 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SREBF2-AS1	NR_157279.2	n.1116C>G		non_coding_transcript_exon_variant	2/2
SREBF2	NM_004599.4			upstream_gene_variant		ENST00000361204.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SREBF2-AS1	ENST00000333487.2	n.1116C>G		non_coding_transcript_exon_variant	2/2	2
SREBF2	ENST00000361204.9			upstream_gene_variant		1	NM_004599.4	P3

Frequencies

GnomAD3 genomes AF: 0.0702 AC: 10622 AN: 151310 Hom.: 534 Cov.: 31

Gnomad AFR AF: 0.0172

Gnomad AMI AF: 0.0929

Gnomad AMR AF: 0.0428

Gnomad ASJ AF: 0.0850

Gnomad EAS AF: 0.000589

Gnomad SAS AF: 0.0455

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.109

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.0618

GnomAD4 exome AF: 0.0862 AC: 27380 AN: 317590 Hom.: 1413 Cov.: 4 AF XY: 0.0859 AC XY: 14209 AN XY: 165384

Gnomad4 AFR exome AF: 0.0179

Gnomad4 AMR exome AF: 0.0445

Gnomad4 ASJ exome AF: 0.0818

Gnomad4 EAS exome AF: 0.000218

Gnomad4 SAS exome AF: 0.0443

Gnomad4 FIN exome AF: 0.131

Gnomad4 NFE exome AF: 0.0996

Gnomad4 OTH exome AF: 0.0764

GnomAD4 genome AF: 0.0701 AC: 10616 AN: 151414 Hom.: 534 Cov.: 31 AF XY: 0.0700 AC XY: 5179 AN XY: 74030

Gnomad4 AFR AF: 0.0171

Gnomad4 AMR AF: 0.0428

Gnomad4 ASJ AF: 0.0850

Gnomad4 EAS AF: 0.000591

Gnomad4 SAS AF: 0.0452

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.0612

Alfa AF: 0.0355 Hom.: 40

Bravo AF: 0.0601

Asia WGS AF: 0.0230 AC: 81 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 17, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
Cadd	Benign	18
Dann	Benign	0.95

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs41277471; hg19: chr22-42229092;