rs7454

Positions:

• chr7-45893407-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000596.4(IGFBP1):​c.*316C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0348 in 153,260 control chromosomes in the GnomAD database, including 135 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 0.035 (135 hom., cov: 33)
  • Exomes 𝑓: 0.025 (0 hom.)
• Consequence: IGFBP1 NM_000596.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.751

Genes affected

IGFBP1 (HGNC:5469): (insulin like growth factor binding protein 1) This gene is a member of the insulin-like growth factor binding protein (IGFBP) family and encodes a protein with an IGFBP N-terminal domain and a thyroglobulin type-I domain. The encoded protein, mainly expressed in the liver, circulates in the plasma and binds both insulin-like growth factors (IGFs) I and II, prolonging their half-lives and altering their interaction with cell surface receptors. This protein is important in cell migration and metabolism. Low levels of this protein may be associated with impaired glucose tolerance, vascular disease and hypertension in human patients. [provided by RefSeq, Aug 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0348 (5302/152232) while in subpopulation AMR AF= 0.0492 (752/15292). AF 95% confidence interval is 0.0463. There are 135 homozygotes in gnomad4. There are 2615 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 135 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGFBP1	NM_000596.4	c.*316C>G		3_prime_UTR_variant	4/4	ENST00000275525.8	NP_000587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGFBP1	ENST00000275525.8	c.*316C>G		3_prime_UTR_variant	4/4	1	NM_000596.4	ENSP00000275525.3
IGFBP1	ENST00000457280.5	c.*316C>G		3_prime_UTR_variant	4/4	5		ENSP00000413511.1
IGFBP1	ENST00000468955.1	c.*316C>G		3_prime_UTR_variant	3/3	5		ENSP00000417069.1

Frequencies

GnomAD3 genomes AF: 0.0348 AC: 5293 AN: 152114 Hom.: 131 Cov.: 33

Gnomad AFR AF: 0.0126

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0484

Gnomad ASJ AF: 0.00980

Gnomad EAS AF: 0.00251

Gnomad SAS AF: 0.0396

Gnomad FIN AF: 0.0555

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0458

Gnomad OTH AF: 0.0239

GnomAD4 exome AF: 0.0253 AC: 26 AN: 1028 Hom.: 0 Cov.: 0 AF XY: 0.0189 AC XY: 11 AN XY: 582

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0323

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0288

Gnomad4 OTH exome AF: 0.0417

GnomAD4 genome AF: 0.0348 AC: 5302 AN: 152232 Hom.: 135 Cov.: 33 AF XY: 0.0351 AC XY: 2615 AN XY: 74434

Gnomad4 AFR AF: 0.0126

Gnomad4 AMR AF: 0.0492

Gnomad4 ASJ AF: 0.00980

Gnomad4 EAS AF: 0.00251

Gnomad4 SAS AF: 0.0392

Gnomad4 FIN AF: 0.0555

Gnomad4 NFE AF: 0.0457

Gnomad4 OTH AF: 0.0237

Alfa AF: 0.0391 Hom.: 14

Bravo AF: 0.0352

Asia WGS AF: 0.0270 AC: 95 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.2
DANN	Benign	0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.97

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: rs7454; hg19: chr7-45933006;