rs3276

chr2-216672275-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_000599.4(IGFBP5):c.*4476C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0627 in 147,176 control chromosomes in the GnomAD database, including 384 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 0.063 (384 hom., cov: 31)
  • Exomes 𝑓: 0.056 (0 hom.)
• Consequence: IGFBP5 NM_000599.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.80

Genes affected

IGFBP5 (HGNC:5474): (insulin like growth factor binding protein 5) Enables insulin-like growth factor I binding activity. Involved in several processes, including cellular response to cAMP; regulation of smooth muscle cell migration; and regulation of smooth muscle cell proliferation. Part of insulin-like growth factor ternary complex. Biomarker of pulmonary fibrosis. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0964 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGFBP5	NM_000599.4	c.*4476C>T		3_prime_UTR_variant	4/4	ENST00000233813.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGFBP5	ENST00000233813.5	c.*4476C>T		3_prime_UTR_variant	4/4	1	NM_000599.4	P1

Frequencies

GnomAD3 genomes AF: 0.0626 AC: 9199 AN: 147016 Hom.: 377 Cov.: 31

Gnomad AFR AF: 0.0983

Gnomad AMI AF: 0.119

Gnomad AMR AF: 0.0495

Gnomad ASJ AF: 0.0292

Gnomad EAS AF: 0.0698

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0261

Gnomad MID AF: 0.0261

Gnomad NFE AF: 0.0472

Gnomad OTH AF: 0.0531

GnomAD4 exome AF: 0.0556 AC: 8 AN: 144 Hom.: 0 Cov.: 0 AF XY: 0.0625 AC XY: 6 AN XY: 96

Gnomad4 FIN exome AF: 0.0493

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.0627 AC: 9226 AN: 147032 Hom.: 384 Cov.: 31 AF XY: 0.0615 AC XY: 4391 AN XY: 71366

Gnomad4 AFR AF: 0.0990

Gnomad4 AMR AF: 0.0497

Gnomad4 ASJ AF: 0.0292

Gnomad4 EAS AF: 0.0694

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.0261

Gnomad4 NFE AF: 0.0472

Gnomad4 OTH AF: 0.0524

Alfa AF: 0.0555 Hom.: 76

Bravo AF: 0.0669

Asia WGS AF: 0.0830 AC: 286 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
Cadd	Benign	15
Dann	Benign	0.93

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: rs3276; hg19: chr2-217536998;