22-41839348-C-T

Variant names:

• chr22-41839348-C-T
• rs9607850
• NM_004599.4:c.88+5990C>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+5990C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 151,768 control chromosomes in the GnomAD database, including 13,388 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 0.42 (13388 hom., cov: 30)
• Consequence: SREBF2 NM_004599.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.39
• Publications: 18 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SREBF2	NM_004599.4	c.88+5990C>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+5990C>T		intron_variant	Intron 1 of 18	1	NM_004599.4	ENSP00000354476.4
SREBF2	ENST00000424354.5	n.88+5990C>T		intron_variant	Intron 1 of 21	1		ENSP00000395728.1
SREBF2	ENST00000710853.1	c.-3+5321C>T		intron_variant	Intron 1 of 18			ENSP00000518526.1

Frequencies

GnomAD3 genomes AF: 0.415 AC: 62972 AN: 151650 Hom.: 13369 Cov.: 30

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.428

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

GnomAD4 genome AF: 0.415 AC: 63025 AN: 151768 Hom.: 13388 Cov.: 30 AF XY: 0.412 AC XY: 30582 AN XY: 74178

African (AFR) AF: 0.407 AC: 16823 AN: 41316

American (AMR) AF: 0.316 AC: 4832 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.336 AC: 1166 AN: 3470

East Asian (EAS) AF: 0.272 AC: 1403 AN: 5158

South Asian (SAS) AF: 0.428 AC: 2057 AN: 4804

European-Finnish (FIN) AF: 0.459 AC: 4836 AN: 10528

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.449 AC: 30478 AN: 67910

Other (OTH) AF: 0.435 AC: 916 AN: 2104

Alfa AF: 0.423 Hom.: 27804

Bravo AF: 0.401

Asia WGS AF: 0.405 AC: 1406 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.10
DANN	Benign	0.27
PhyloP100		-2.4
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: rs9607850; hg19: chr22-42235352;