22-41871192-C-T

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.867+157C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0971 in 152,106 control chromosomes in the GnomAD database, including 1,163 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.097 (1163 hom., cov: 31)
• Consequence: SREBF2 NM_004599.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.965

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=-0.92).
• BP6: Variant 22-41871192-C-T is Benign according to our data. Variant chr22-41871192-C-T is described in ClinVar as [Benign]. Clinvar id is 1283366.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SREBF2	NM_004599.4	c.867+157C>T		intron_variant		ENST00000361204.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SREBF2	ENST00000361204.9	c.867+157C>T		intron_variant		1	NM_004599.4	P3
SREBF2	ENST00000424354.5	c.867+157C>T		intron_variant, NMD_transcript_variant		1
SREBF2	ENST00000710853.1	c.777+157C>T		intron_variant				A2

Frequencies

GnomAD3 genomes AF: 0.0969 AC: 14732 AN: 151986 Hom.: 1152 Cov.: 31

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.0989

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.0680

Gnomad EAS AF: 0.0268

Gnomad SAS AF: 0.0586

Gnomad FIN AF: 0.0235

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0427

Gnomad OTH AF: 0.0837

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

GnomAD4 genome AF: 0.0971 AC: 14777 AN: 152106 Hom.: 1163 Cov.: 31 AF XY: 0.0946 AC XY: 7035 AN XY: 74362

Gnomad4 AFR AF: 0.220

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.0680

Gnomad4 EAS AF: 0.0268

Gnomad4 SAS AF: 0.0583

Gnomad4 FIN AF: 0.0235

Gnomad4 NFE AF: 0.0427

Gnomad4 OTH AF: 0.0828

Alfa AF: 0.0738 Hom.: 101

Bravo AF: 0.108

Asia WGS AF: 0.0600 AC: 208 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 17, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.66
Dann	Benign	0.67

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: rs9607853; hg19: chr22-42267196;