rs2297508

Variant names:

• chr17-17812003-C-G
• rs2297508
• NM_004176.5:c.*619G>C

Your query was ambiguous. Multiple possible variants found:

• chr17-17812003-C-G
• chr17-17812003-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004176.5(SREBF1):​c.*619G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 437,516 control chromosomes in the GnomAD database, including 68,804 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 0.57 (25617 hom., cov: 33)
  • Exomes 𝑓: 0.53 (43187 hom.)
• Consequence: SREBF1 NM_004176.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0240
• Publications: 60 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, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• Hirschsprung disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SREBF1	NM_004176.5	c.*619G>C		3_prime_UTR_variant	Exon 19 of 19	ENST00000261646.11	NP_004167.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SREBF1	ENST00000261646.11	c.*619G>C		3_prime_UTR_variant	Exon 19 of 19	1	NM_004176.5	ENSP00000261646.5

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86684 AN: 151876 Hom.: 25589 Cov.: 33

Gnomad AFR AF: 0.580

Gnomad AMI AF: 0.553

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.590

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.634

Gnomad OTH AF: 0.575

GnomAD2 exomes AF: 0.498 AC: 59899 AN: 120346 AF XY: 0.493

Gnomad AFR exome AF: 0.570

Gnomad AMR exome AF: 0.396

Gnomad ASJ exome AF: 0.585

Gnomad EAS exome AF: 0.140

Gnomad FIN exome AF: 0.594

Gnomad NFE exome AF: 0.631

Gnomad OTH exome AF: 0.530

GnomAD4 exome AF: 0.529 AC: 150938 AN: 285520 Hom.: 43187 Cov.: 0 AF XY: 0.509 AC XY: 83622 AN XY: 164168

African (AFR) AF: 0.574 AC: 3984 AN: 6936

American (AMR) AF: 0.390 AC: 8421 AN: 21608

Ashkenazi Jewish (ASJ) AF: 0.582 AC: 5888 AN: 10114

East Asian (EAS) AF: 0.152 AC: 1214 AN: 7964

South Asian (SAS) AF: 0.318 AC: 18074 AN: 56812

European-Finnish (FIN) AF: 0.602 AC: 7544 AN: 12534

Middle Eastern (MID) AF: 0.562 AC: 1531 AN: 2726

European-Non Finnish (NFE) AF: 0.630 AC: 96583 AN: 153414

Other (OTH) AF: 0.574 AC: 7699 AN: 13412

GnomAD4 genome AF: 0.571 AC: 86772 AN: 151996 Hom.: 25617 Cov.: 33 AF XY: 0.559 AC XY: 41497 AN XY: 74274

African (AFR) AF: 0.580 AC: 24053 AN: 41470

American (AMR) AF: 0.476 AC: 7273 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.590 AC: 2049 AN: 3470

East Asian (EAS) AF: 0.154 AC: 791 AN: 5120

South Asian (SAS) AF: 0.310 AC: 1489 AN: 4810

European-Finnish (FIN) AF: 0.582 AC: 6150 AN: 10574

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.634 AC: 43055 AN: 67938

Other (OTH) AF: 0.577 AC: 1220 AN: 2114

Alfa AF: 0.542 Hom.: 3164

Bravo AF: 0.564

Asia WGS AF: 0.304 AC: 1059 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.6
DANN	Benign	0.43
PhyloP100		-0.024
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2297508; hg19: chr17-17715317; COSMIC: COSV55397229;