rs2241193

chr2-216689490-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+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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
IGFBP5	NM_000599.4	c.337+4949A>G		intron_variant		ENST00000233813.5
LOC124900515	XR_007088080.1	n.1047A>G		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGFBP5	ENST00000233813.5	c.337+4949A>G		intron_variant		1	NM_000599.4	P1
IGFBP5	ENST00000449583.1	c.337+4949A>G		intron_variant		3
IGFBP5	ENST00000486341.1	n.229+4949A>G		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.784

Gnomad4 AMR AF: 0.766

Gnomad4 ASJ AF: 0.830

Gnomad4 EAS AF: 0.758

Gnomad4 SAS AF: 0.843

Gnomad4 FIN AF: 0.823

Gnomad4 NFE AF: 0.867

Gnomad4 OTH AF: 0.804

Alfa AF: 0.856 Hom.: 89331

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

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: rs2241193; hg19: chr2-217554213;