Variant rs12601420 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004176.5(SREBF1):c.1069-48G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0273 in 1,476,608 control chromosomes in the GnomAD database, including 2,035 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 0.030 ( 295 hom., cov: 31)

Exomes 𝑓: 0.027 ( 1740 hom. )

Consequence

SREBF1
NM_004176.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.437

Variant links:

Genes affected

SREBF1 (HGNC:11289): (sterol regulatory element binding transcription factor 1) This gene encodes a basic helix-loop-helix-leucine zipper (bHLH-Zip) transcription factor that binds to the sterol regulatory element-1 (SRE1), which is a motif that is found in the promoter of the low density lipoprotein receptor gene and other genes involved in sterol biosynthesis. The encoded protein is synthesized as a precursor that is initially attached to the nuclear membrane and endoplasmic reticulum. Following cleavage, the mature protein translocates to the nucleus and activates transcription. This cleaveage is inhibited by sterols. This gene is located within the Smith-Magenis syndrome region on chromosome 17. Alternative promoter usage and splicing result in multiple transcript variants, including SREBP-1a and SREBP-1c, which correspond to RefSeq transcript variants 2 and 3, respectively. [provided by RefSeq, Nov 2017]

SREBF1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SREBF1	NM_004176.5 linkuse as main transcript	c.1069-48G>A		intron_variant		ENST00000261646.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SREBF1	ENST00000261646.11 linkuse as main transcript	c.1069-48G>A		intron_variant		1	NM_004176.5	P4	P36956-1

Frequencies

GnomAD3 genomes

AF:

0.0301

AC:

4563

AN:

151688

Hom.:

292

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00723

Gnomad AMI

AF:

0.00220

Gnomad AMR

AF:

0.0859

Gnomad ASJ

AF:

0.0164

Gnomad EAS

AF:

0.273

Gnomad SAS

AF:

0.0150

Gnomad FIN

AF:

0.0303

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0152

Gnomad OTH

AF:

0.0293

GnomAD3 exomes

AF:

0.0513

AC:

12244

AN:

238444

Hom.:

987

AF XY:

0.0454

AC XY:

5857

AN XY:

129096

show subpopulations

Gnomad AFR exome

AF:

0.00686

Gnomad AMR exome

AF:

0.117

Gnomad ASJ exome

AF:

0.0190

Gnomad EAS exome

AF:

0.290

Gnomad SAS exome

AF:

0.0113

Gnomad FIN exome

AF:

0.0307

Gnomad NFE exome

AF:

0.0168

Gnomad OTH exome

AF:

0.0366

GnomAD4 exome

AF:

0.0270

AC:

35807

AN:

1324802

Hom.:

1740

Cov.:

AF XY:

0.0257

AC XY:

17083

AN XY:

665598

show subpopulations

Gnomad4 AFR exome

AF:

0.00496

Gnomad4 AMR exome

AF:

0.116

Gnomad4 ASJ exome

AF:

0.0196

Gnomad4 EAS exome

AF:

0.236

Gnomad4 SAS exome

AF:

0.0119

Gnomad4 FIN exome

AF:

0.0301

Gnomad4 NFE exome

AF:

0.0165

Gnomad4 OTH exome

AF:

0.0356

GnomAD4 genome

AF:

0.0301

AC:

4571

AN:

151806

Hom.:

295

Cov.:

AF XY:

0.0327

AC XY:

2422

AN XY:

74166

show subpopulations

Gnomad4 AFR

AF:

0.00720

Gnomad4 AMR

AF:

0.0868

Gnomad4 ASJ

AF:

0.0164

Gnomad4 EAS

AF:

0.273

Gnomad4 SAS

AF:

0.0150

Gnomad4 FIN

AF:

0.0303

Gnomad4 NFE

AF:

0.0152

Gnomad4 OTH

AF:

0.0281

Alfa

AF:

0.0211

Hom.:

Bravo

AF:

0.0372

Asia WGS

AF:

0.118

AC:

410

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

6.9

DANN

Benign

0.42

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over