chr2-216674446-C-A

Position:

• chr2-216674446-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000233813.5(IGFBP5):​c.*2305G>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 0.0589 in 152,586 control chromosomes in the GnomAD database, including 380 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 0.059 (380 hom., cov: 32)
  • Exomes 𝑓: 0.042 (0 hom.)
• Consequence: IGFBP5 ENST00000233813.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.629

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGFBP5	NM_000599.4	c.*2305G>T		3_prime_UTR_variant	4/4	ENST00000233813.5	NP_000590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGFBP5	ENST00000233813.5	c.*2305G>T		3_prime_UTR_variant	4/4	1	NM_000599.4	ENSP00000233813	P1

Frequencies

GnomAD3 genomes AF: 0.0587 AC: 8936 AN: 152114 Hom.: 370 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.0498

Gnomad ASJ AF: 0.0167

Gnomad EAS AF: 0.0750

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0244

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0349

Gnomad OTH AF: 0.0474

GnomAD4 exome AF: 0.0424 AC: 15 AN: 354 Hom.: 0 Cov.: 0 AF XY: 0.0446 AC XY: 9 AN XY: 202

Gnomad4 FIN exome AF: 0.0452

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0590 AC: 8978 AN: 152232 Hom.: 380 Cov.: 32 AF XY: 0.0585 AC XY: 4358 AN XY: 74452

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.0499

Gnomad4 ASJ AF: 0.0167

Gnomad4 EAS AF: 0.0745

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.0244

Gnomad4 NFE AF: 0.0349

Gnomad4 OTH AF: 0.0464

Alfa AF: 0.0465 Hom.: 21

Bravo AF: 0.0609

Asia WGS AF: 0.0830 AC: 287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.8
DANN	Benign	0.79

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: rs13403592; hg19: chr2-217539169;