rs3770472

Variant names:

• chr2-216694012-T-C
• rs3770472
• NM_000599.4:c.337+427A>G

Variant summary

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

The NM_000599.4(IGFBP5):​c.337+427A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 110,468 control chromosomes in the GnomAD database, including 3,121 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 0.25 (3121 hom., cov: 30)
• Consequence: IGFBP5 NM_000599.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.276
• Publications: 10 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000599.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGFBP5	NM_000599.4	MANE Select	c.337+427A>G		intron	N/A	NP_000590.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGFBP5	ENST00000233813.5	TSL:1 MANE Select	c.337+427A>G		intron	N/A	ENSP00000233813.4
	IGFBP5	ENST00000449583.1	TSL:3	c.337+427A>G		intron	N/A	ENSP00000413474.1
	IGFBP5	ENST00000486341.1	TSL:2	n.229+427A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.254 AC: 28056 AN: 110342 Hom.: 3121 Cov.: 30

Gnomad AFR AF: 0.0727

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.277

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.254 AC: 28068 AN: 110468 Hom.: 3121 Cov.: 30 AF XY: 0.253 AC XY: 13435 AN XY: 53048

African (AFR) AF: 0.0726 AC: 2676 AN: 36852

American (AMR) AF: 0.274 AC: 2953 AN: 10768

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 803 AN: 2408

East Asian (EAS) AF: 0.244 AC: 682 AN: 2798

South Asian (SAS) AF: 0.320 AC: 697 AN: 2176

European-Finnish (FIN) AF: 0.362 AC: 2274 AN: 6276

Middle Eastern (MID) AF: 0.276 AC: 59 AN: 214

European-Non Finnish (NFE) AF: 0.368 AC: 17270 AN: 46886

Other (OTH) AF: 0.276 AC: 412 AN: 1492

Alfa AF: 0.237 Hom.: 8641

Bravo AF: 0.178

Asia WGS AF: 0.127 AC: 443 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	18
DANN	Benign	0.78
PhyloP100		0.28
Mutation Taster		=100/0	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: rs3770472; hg19: chr2-217558735;