chr22-41868265-G-T

Position:

• chr22-41868265-G-T

Variant summary

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

The NM_004599.4(SREBF2):​c.539-346G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 151,976 control chromosomes in the GnomAD database, including 12,413 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 0.37 (12413 hom., cov: 32)
• Consequence: SREBF2 NM_004599.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.61

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SREBF2	NM_004599.4	c.539-346G>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.539-346G>T		intron_variant		1	NM_004599.4	ENSP00000354476.4
SREBF2	ENST00000424354.5	n.539-346G>T		intron_variant		1		ENSP00000395728.1
SREBF2	ENST00000710853.1	c.449-346G>T		intron_variant				ENSP00000518526.1

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56234 AN: 151858 Hom.: 12372 Cov.: 32

Gnomad AFR AF: 0.574

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.355

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

GnomAD4 genome AF: 0.371 AC: 56335 AN: 151976 Hom.: 12413 Cov.: 32 AF XY: 0.369 AC XY: 27449 AN XY: 74294

Gnomad4 AFR AF: 0.575

Gnomad4 AMR AF: 0.513

Gnomad4 ASJ AF: 0.366

Gnomad4 EAS AF: 0.233

Gnomad4 SAS AF: 0.362

Gnomad4 FIN AF: 0.196

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.351

Alfa AF: 0.255 Hom.: 2158

Bravo AF: 0.407

Asia WGS AF: 0.322 AC: 1120 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.012
DANN	Benign	0.63

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: rs2269657; hg19: chr22-42264269;