2-216694012-T-C

Position:

• chr2-216694012-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

IGFBP5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGFBP5	NM_000599.4	c.337+427A>G		intron_variant		ENST00000233813.5	NP_000590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGFBP5	ENST00000233813.5	c.337+427A>G		intron_variant		1	NM_000599.4	ENSP00000233813.4
IGFBP5	ENST00000449583.1	c.337+427A>G		intron_variant		3		ENSP00000413474.1
IGFBP5	ENST00000486341.1	n.229+427A>G		intron_variant		2

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

Gnomad4 AFR AF: 0.0726

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.333

Gnomad4 EAS AF: 0.244

Gnomad4 SAS AF: 0.320

Gnomad4 FIN AF: 0.362

Gnomad4 NFE AF: 0.368

Gnomad4 OTH AF: 0.276

Alfa AF: 0.241 Hom.: 6420

Bravo AF: 0.178

Asia WGS AF: 0.127 AC: 443 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	18
DANN	Benign	0.78

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: rs3770472; hg19: chr2-217558735;