chr22-41891450-A-G

Position:

• chr22-41891450-A-G

Variant summary

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

The NM_004599.4(SREBF2):​c.2209-1667A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.666 in 151,982 control chromosomes in the GnomAD database, including 34,247 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 0.67 (34245 hom., cov: 31)
  • Exomes 𝑓: 0.64 (2 hom.)
• Consequence: SREBF2 NM_004599.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SREBF2	NM_004599.4	c.2209-1667A>G		intron_variant		ENST00000361204.9	NP_004590.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SREBF2	ENST00000361204.9	c.2209-1667A>G		intron_variant		1	NM_004599.4	ENSP00000354476	P3
SREBF2	ENST00000424354.5	c.*254-1667A>G		intron_variant, NMD_transcript_variant		1		ENSP00000395728
SREBF2	ENST00000491541.1	n.759+51A>G		intron_variant, non_coding_transcript_variant		1
SREBF2	ENST00000710853.1	c.2119-1667A>G		intron_variant				ENSP00000518526	A2

Frequencies

GnomAD3 genomes AF: 0.666 AC: 101117 AN: 151850 Hom.: 34199 Cov.: 31

Gnomad AFR AF: 0.770

Gnomad AMI AF: 0.694

Gnomad AMR AF: 0.712

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.681

Gnomad SAS AF: 0.579

Gnomad FIN AF: 0.599

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.607

GnomAD4 exome AF: 0.643 AC: 9 AN: 14 Hom.: 2 AF XY: 0.600 AC XY: 6 AN XY: 10

Gnomad4 FIN exome AF: 0.667

Gnomad4 NFE exome AF: 0.667

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.666 AC: 101214 AN: 151968 Hom.: 34245 Cov.: 31 AF XY: 0.665 AC XY: 49408 AN XY: 74280

Gnomad4 AFR AF: 0.770

Gnomad4 AMR AF: 0.713

Gnomad4 ASJ AF: 0.652

Gnomad4 EAS AF: 0.680

Gnomad4 SAS AF: 0.578

Gnomad4 FIN AF: 0.599

Gnomad4 NFE AF: 0.610

Gnomad4 OTH AF: 0.605

Alfa AF: 0.626 Hom.: 16153

Bravo AF: 0.684

Asia WGS AF: 0.626 AC: 2176 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	0.32
DANN	Benign	0.66

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: rs2267443; hg19: chr22-42287454;