rs5996080

Positions:

• chr22-41893462-T-C
• chr22-41893462-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004599.4(SREBF2):​c.2377+177T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,126 control chromosomes in the GnomAD database, including 2,213 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.14 (2213 hom., cov: 32)
• Consequence: SREBF2 NM_004599.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.45

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 22-41893462-T-C is Benign according to our data. Variant chr22-41893462-T-C is described in ClinVar as [Benign]. Clinvar id is 1289993.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SREBF2	NM_004599.4	c.2377+177T>C		intron_variant		ENST00000361204.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SREBF2	ENST00000361204.9	c.2377+177T>C		intron_variant		1	NM_004599.4	P3
SREBF2	ENST00000424354.5	c.*422+177T>C		intron_variant, NMD_transcript_variant		1
SREBF2	ENST00000491541.1	n.928+177T>C		intron_variant, non_coding_transcript_variant		1
SREBF2	ENST00000710853.1	c.2287+177T>C		intron_variant				A2

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21264 AN: 152008 Hom.: 2205 Cov.: 32

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.0385

Gnomad AMR AF: 0.0840

Gnomad ASJ AF: 0.0588

Gnomad EAS AF: 0.0729

Gnomad SAS AF: 0.0781

Gnomad FIN AF: 0.0774

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0822

Gnomad OTH AF: 0.113

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

GnomAD4 genome AF: 0.140 AC: 21306 AN: 152126 Hom.: 2213 Cov.: 32 AF XY: 0.137 AC XY: 10205 AN XY: 74374

Gnomad4 AFR AF: 0.298

Gnomad4 AMR AF: 0.0838

Gnomad4 ASJ AF: 0.0588

Gnomad4 EAS AF: 0.0732

Gnomad4 SAS AF: 0.0780

Gnomad4 FIN AF: 0.0774

Gnomad4 NFE AF: 0.0822

Gnomad4 OTH AF: 0.111

Alfa AF: 0.0826 Hom.: 888

Bravo AF: 0.148

Asia WGS AF: 0.0920 AC: 318 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.92
DANN	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs5996080; hg19: chr22-42289466;