chr22-41838933-C-T

Position:

• chr22-41838933-C-T

Variant summary

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

The NM_004599.4(SREBF2):​c.88+5575C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 151,826 control chromosomes in the GnomAD database, including 29,904 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 0.62 (29904 hom., cov: 30)
• Consequence: SREBF2 NM_004599.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.455

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SREBF2	NM_004599.4	c.88+5575C>T		intron_variant		ENST00000361204.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SREBF2	ENST00000361204.9	c.88+5575C>T		intron_variant		1	NM_004599.4	P3
SREBF2	ENST00000424354.5	c.88+5575C>T		intron_variant, NMD_transcript_variant		1
SREBF2	ENST00000710853.1	c.-3+4906C>T		intron_variant				A2

Frequencies

GnomAD3 genomes AF: 0.617 AC: 93678 AN: 151708 Hom.: 29858 Cov.: 30

Gnomad AFR AF: 0.772

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.661

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.627

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

GnomAD4 genome AF: 0.618 AC: 93778 AN: 151826 Hom.: 29904 Cov.: 30 AF XY: 0.618 AC XY: 45837 AN XY: 74170

Gnomad4 AFR AF: 0.772

Gnomad4 AMR AF: 0.661

Gnomad4 ASJ AF: 0.539

Gnomad4 EAS AF: 0.328

Gnomad4 SAS AF: 0.571

Gnomad4 FIN AF: 0.591

Gnomad4 NFE AF: 0.548

Gnomad4 OTH AF: 0.631

Alfa AF: 0.588 Hom.: 5246

Bravo AF: 0.633

Asia WGS AF: 0.523 AC: 1820 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.6
DANN	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs7287010; hg19: chr22-42234937;