rs3276

Variant names:

• chr2-216672275-G-A
• rs3276
• NM_000599.4:c.*4476C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
IGFBP5	NM_000599.4	c.*4476C>T		3_prime_UTR_variant	Exon 4 of 4	ENST00000233813.5	NP_000590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGFBP5	ENST00000233813.5	c.*4476C>T		3_prime_UTR_variant	Exon 4 of 4	1	NM_000599.4	ENSP00000233813.4

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.0493 AC: 7 AN: 142

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.0990 AC: 3939 AN: 39796

American (AMR) AF: 0.0497 AC: 735 AN: 14800

Ashkenazi Jewish (ASJ) AF: 0.0292 AC: 101 AN: 3458

East Asian (EAS) AF: 0.0694 AC: 351 AN: 5056

South Asian (SAS) AF: 0.101 AC: 472 AN: 4652

European-Finnish (FIN) AF: 0.0261 AC: 226 AN: 8668

Middle Eastern (MID) AF: 0.0250 AC: 7 AN: 280

European-Non Finnish (NFE) AF: 0.0472 AC: 3180 AN: 67370

Other (OTH) AF: 0.0524 AC: 107 AN: 2042

Alfa AF: 0.0525 Hom.: 140

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
PhyloP100		2.8
Mutation Taster		=95/5	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: rs3276; hg19: chr2-217536998;