chr22-41844793-C-T

Variant names:

• chr22-41844793-C-T
• rs2284082
• NM_004599.4:c.88+11435C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004599.4(SREBF2):​c.88+11435C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.738 in 151,912 control chromosomes in the GnomAD database, including 41,808 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 0.74 (41808 hom., cov: 30)
• Consequence: SREBF2 NM_004599.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.303
• 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]

SREBF2 Gene-Disease associations (from GenCC):

• multiple congenital anomalies/dysmorphic syndrome

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• hereditary spastic paraplegia

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SREBF2	NM_004599.4	c.88+11435C>T		intron_variant	Intron 1 of 18	ENST00000361204.9	NP_004590.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SREBF2	ENST00000361204.9	c.88+11435C>T		intron_variant	Intron 1 of 18	1	NM_004599.4	ENSP00000354476.4
SREBF2	ENST00000424354.5	n.88+11435C>T		intron_variant	Intron 1 of 21	1		ENSP00000395728.1
SREBF2	ENST00000710853.1	c.-3+10766C>T		intron_variant	Intron 1 of 18			ENSP00000518526.1

Frequencies

GnomAD3 genomes AF: 0.737 AC: 111937 AN: 151794 Hom.: 41743 Cov.: 30

Gnomad AFR AF: 0.815

Gnomad AMI AF: 0.769

Gnomad AMR AF: 0.811

Gnomad ASJ AF: 0.705

Gnomad EAS AF: 0.518

Gnomad SAS AF: 0.763

Gnomad FIN AF: 0.680

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.747

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

GnomAD4 genome AF: 0.738 AC: 112065 AN: 151912 Hom.: 41808 Cov.: 30 AF XY: 0.738 AC XY: 54787 AN XY: 74246

African (AFR) AF: 0.815 AC: 33774 AN: 41426

American (AMR) AF: 0.811 AC: 12384 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.705 AC: 2444 AN: 3468

East Asian (EAS) AF: 0.518 AC: 2664 AN: 5142

South Asian (SAS) AF: 0.763 AC: 3670 AN: 4810

European-Finnish (FIN) AF: 0.680 AC: 7171 AN: 10544

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.699 AC: 47464 AN: 67936

Other (OTH) AF: 0.750 AC: 1582 AN: 2108

Alfa AF: 0.718 Hom.: 5124

Bravo AF: 0.752

Asia WGS AF: 0.704 AC: 2444 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.3
DANN	Benign	0.33
PhyloP100		-0.30
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs2284082; hg19: chr22-42240797;