22-41873624-C-T

Position:

• chr22-41873624-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004599.4(SREBF2):​c.868-174C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 655,314 control chromosomes in the GnomAD database, including 18,443 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (3995 hom., cov: 32)
  • Exomes 𝑓: 0.23 (14448 hom.)
• Consequence: SREBF2 NM_004599.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.59

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 22-41873624-C-T is Benign according to our data. Variant chr22-41873624-C-T is described in ClinVar as [Benign]. Clinvar id is 1287095.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SREBF2	NM_004599.4	c.868-174C>T		intron_variant		ENST00000361204.9	NP_004590.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SREBF2	ENST00000361204.9	c.868-174C>T		intron_variant		1	NM_004599.4	ENSP00000354476	P3
SREBF2	ENST00000424354.5	c.868-174C>T		intron_variant, NMD_transcript_variant		1		ENSP00000395728
SREBF2	ENST00000710853.1	c.778-174C>T		intron_variant				ENSP00000518526	A2

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33292 AN: 151842 Hom.: 3998 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.487

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.208

GnomAD4 exome AF: 0.231 AC: 116063 AN: 503354 Hom.: 14448 AF XY: 0.230 AC XY: 61367 AN XY: 266756

Gnomad4 AFR exome AF: 0.184

Gnomad4 AMR exome AF: 0.109

Gnomad4 ASJ exome AF: 0.238

Gnomad4 EAS exome AF: 0.397

Gnomad4 SAS exome AF: 0.190

Gnomad4 FIN exome AF: 0.217

Gnomad4 NFE exome AF: 0.235

Gnomad4 OTH exome AF: 0.231

GnomAD4 genome AF: 0.219 AC: 33284 AN: 151960 Hom.: 3995 Cov.: 32 AF XY: 0.218 AC XY: 16176 AN XY: 74276

Gnomad4 AFR AF: 0.182

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.487

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.233

Gnomad4 NFE AF: 0.236

Gnomad4 OTH AF: 0.207

Alfa AF: 0.203 Hom.: 1332

Bravo AF: 0.212

Asia WGS AF: 0.275 AC: 957 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 15, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.022
DANN	Benign	0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs133291; hg19: chr22-42269628;