Variant 22-41866943-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_004599.4(SREBF2):c.201T>C(p.Ser67=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000415 in 1,613,522 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0024 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00021 ( 2 hom. )

Consequence

SREBF2
NM_004599.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.560

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 22-41866943-T-C is Benign according to our data. Variant chr22-41866943-T-C is described in ClinVar as [Benign]. Clinvar id is 786383.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.56 with no splicing effect.

BS2

High AC in GnomAd4 at 359 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SREBF2	NM_004599.4 linkuse as main transcript	c.201T>C	p.Ser67=	synonymous_variant	2/19	ENST00000361204.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SREBF2	ENST00000361204.9 linkuse as main transcript	c.201T>C	p.Ser67=	synonymous_variant	2/19	1	NM_004599.4	P3	Q12772-1
SREBF2	ENST00000424354.5 linkuse as main transcript	c.201T>C	p.Ser67=	synonymous_variant, NMD_transcript_variant	2/22	1
SREBF2	ENST00000710853.1 linkuse as main transcript	c.111T>C	p.Ser37=	synonymous_variant	2/19			A2

Frequencies

GnomAD3 genomes

AF:

0.00235

AC:

357

AN:

151986

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00803

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000551

AC:

137

AN:

248858

Hom.:

AF XY:

0.000364

AC XY:

AN XY:

134738

show subpopulations

Gnomad AFR exome

AF:

0.00776

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000899

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000212

AC:

310

AN:

1461418

Hom.:

Cov.:

AF XY:

0.000194

AC XY:

141

AN XY:

727004

show subpopulations

Gnomad4 AFR exome

AF:

0.00759

Gnomad4 AMR exome

AF:

0.000268

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000144

Gnomad4 OTH exome

AF:

0.000414

GnomAD4 genome

AF:

0.00236

AC:

359

AN:

152104

Hom.:

Cov.:

AF XY:

0.00204

AC XY:

152

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.00806

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000902

Hom.:

Bravo

AF:

0.00246

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.54

DANN

Benign

0.20

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over