rs5996074

chr22-41840333-G-Achr22-41840333-G-C

Variant summary

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

The NM_004599.4(SREBF2):c.88+6975G>A 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 152,034 control chromosomes in the GnomAD database, including 41,840 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 (41840 hom., cov: 31)
• Consequence: SREBF2 NM_004599.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52

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=-0.95).
• 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/exons	MANE	UniProt
SREBF2	NM_004599.4	c.88+6975G>A		intron_variant		ENST00000361204.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SREBF2	ENST00000361204.9	c.88+6975G>A		intron_variant		1	NM_004599.4	P3
SREBF2	ENST00000424354.5	c.88+6975G>A		intron_variant, NMD_transcript_variant		1
SREBF2	ENST00000710853.1	c.-3+6306G>A		intron_variant				A2

Frequencies

GnomAD3 genomes AF: 0.737 AC: 112028 AN: 151916 Hom.: 41772 Cov.: 31

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: 0.723

Gnomad NFE AF: 0.698

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: 112159 AN: 152034 Hom.: 41840 Cov.: 31 AF XY: 0.738 AC XY: 54833 AN XY: 74314

Gnomad4 AFR AF: 0.816

Gnomad4 AMR AF: 0.811

Gnomad4 ASJ AF: 0.705

Gnomad4 EAS AF: 0.518

Gnomad4 SAS AF: 0.763

Gnomad4 FIN AF: 0.680

Gnomad4 NFE AF: 0.698

Gnomad4 OTH AF: 0.750

Alfa AF: 0.705 Hom.: 5185

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	-0.95
Cadd	Benign	0.088
Dann	Benign	0.20

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: rs5996074; hg19: chr22-42236337;