2-216689490-T-C

Variant names:

• chr2-216689490-T-C
• rs2241193
• NM_000599.4:c.337+4949A>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+4949A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.824 in 152,236 control chromosomes in the GnomAD database, including 51,891 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 0.82 (51891 hom., cov: 34)
• Consequence: IGFBP5 NM_000599.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.537
• Publications: 11 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]

LOC124900515 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.861 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGFBP5	NM_000599.4	c.337+4949A>G		intron_variant	Intron 1 of 3	ENST00000233813.5	NP_000590.1
LOC124900515	XR_007088080.1	n.1047A>G		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGFBP5	ENST00000233813.5	c.337+4949A>G		intron_variant	Intron 1 of 3	1	NM_000599.4	ENSP00000233813.4
IGFBP5	ENST00000449583.1	c.337+4949A>G		intron_variant	Intron 1 of 1	3		ENSP00000413474.1
IGFBP5	ENST00000486341.1	n.229+4949A>G		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.824 AC: 125360 AN: 152118 Hom.: 51871 Cov.: 34

Gnomad AFR AF: 0.784

Gnomad AMI AF: 0.732

Gnomad AMR AF: 0.765

Gnomad ASJ AF: 0.830

Gnomad EAS AF: 0.757

Gnomad SAS AF: 0.843

Gnomad FIN AF: 0.823

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.867

Gnomad OTH AF: 0.807

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

GnomAD4 genome AF: 0.824 AC: 125429 AN: 152236 Hom.: 51891 Cov.: 34 AF XY: 0.822 AC XY: 61135 AN XY: 74418

African (AFR) AF: 0.784 AC: 32540 AN: 41518

American (AMR) AF: 0.766 AC: 11712 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.830 AC: 2878 AN: 3468

East Asian (EAS) AF: 0.758 AC: 3925 AN: 5180

South Asian (SAS) AF: 0.843 AC: 4064 AN: 4822

European-Finnish (FIN) AF: 0.823 AC: 8723 AN: 10600

Middle Eastern (MID) AF: 0.847 AC: 249 AN: 294

European-Non Finnish (NFE) AF: 0.867 AC: 58973 AN: 68032

Other (OTH) AF: 0.804 AC: 1697 AN: 2112

Alfa AF: 0.851 Hom.: 205649

Bravo AF: 0.815

Asia WGS AF: 0.738 AC: 2565 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.7
DANN	Benign	0.82
PhyloP100		-0.54
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: rs2241193; hg19: chr2-217554213;