chr17-17836850-GC-G

Variant names:

• chr17-17836850-GC-G
• rs60282872
• NM_004176.5:c.-34delG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_004176.5(SREBF1):​c.-34delG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.45 (18409 hom., cov: 0)
  • Exomes 𝑓: 0.58 (246776 hom.)
• Consequence: SREBF1 NM_004176.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.687
• Publications: 8 publications found

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 Gene-Disease associations (from GenCC):

• hereditary mucoepithelial dysplasia

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, PanelApp Australia
• IFAP syndrome 2

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: PanelApp Australia, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• Hirschsprung disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004176.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SREBF1	NM_004176.5	MANE Select	c.-34delG		5_prime_UTR	Exon 1 of 19	NP_004167.3
	SREBF1	NM_001005291.3		c.-34delG		5_prime_UTR	Exon 1 of 20	NP_001005291.1	P36956-4
	SREBF1	NM_001388385.1		c.-34delG		5_prime_UTR	Exon 1 of 18	NP_001375314.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SREBF1	ENST00000261646.11	TSL:1 MANE Select	c.-34delG		5_prime_UTR	Exon 1 of 19	ENSP00000261646.5	P36956-1
	SREBF1	ENST00000355815.8	TSL:1	c.-34delG		5_prime_UTR	Exon 1 of 20	ENSP00000348069.4	P36956-4
	SREBF1	ENST00000892469.1		c.-34delG		5_prime_UTR	Exon 1 of 20	ENSP00000562529.1

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68152 AN: 151868 Hom.: 18406 Cov.: 0

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.0728

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.565

Gnomad MID AF: 0.529

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.473

GnomAD2 exomes AF: 0.450 AC: 49433 AN: 109878 AF XY: 0.450

Gnomad AFR exome AF: 0.169

Gnomad AMR exome AF: 0.361

Gnomad ASJ exome AF: 0.546

Gnomad EAS exome AF: 0.0702

Gnomad FIN exome AF: 0.587

Gnomad NFE exome AF: 0.629

Gnomad OTH exome AF: 0.496

GnomAD4 exome AF: 0.585 AC: 795023 AN: 1359966 Hom.: 246776 Cov.: 0 AF XY: 0.576 AC XY: 386536 AN XY: 670768

African (AFR) AF: 0.174 AC: 4914 AN: 28184

American (AMR) AF: 0.368 AC: 12542 AN: 34040

Ashkenazi Jewish (ASJ) AF: 0.548 AC: 13290 AN: 24236

East Asian (EAS) AF: 0.0745 AC: 2465 AN: 33096

South Asian (SAS) AF: 0.279 AC: 21381 AN: 76716

European-Finnish (FIN) AF: 0.585 AC: 19912 AN: 34022

Middle Eastern (MID) AF: 0.481 AC: 2252 AN: 4680

European-Non Finnish (NFE) AF: 0.644 AC: 688165 AN: 1068236

Other (OTH) AF: 0.530 AC: 30102 AN: 56756

GnomAD4 genome AF: 0.449 AC: 68176 AN: 151976 Hom.: 18409 Cov.: 0 AF XY: 0.440 AC XY: 32691 AN XY: 74282

African (AFR) AF: 0.189 AC: 7861 AN: 41508

American (AMR) AF: 0.421 AC: 6434 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 1910 AN: 3468

East Asian (EAS) AF: 0.0726 AC: 374 AN: 5152

South Asian (SAS) AF: 0.268 AC: 1292 AN: 4828

European-Finnish (FIN) AF: 0.565 AC: 5978 AN: 10578

Middle Eastern (MID) AF: 0.531 AC: 155 AN: 292

European-Non Finnish (NFE) AF: 0.629 AC: 42682 AN: 67852

Other (OTH) AF: 0.473 AC: 997 AN: 2106

Alfa AF: 0.466 Hom.: 2485

Bravo AF: 0.429

Asia WGS AF: 0.229 AC: 794 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.69
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs60282872; hg19: chr17-17740164; COSMIC: COSV55420436;