rs11575134

Positions:

• chr2-216691101-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_000599.4(IGFBP5):​c.337+3338G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,100 control chromosomes in the GnomAD database, including 2,482 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 0.17 (2482 hom., cov: 32)
• Consequence: IGFBP5 NM_000599.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.329

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGFBP5	NM_000599.4	c.337+3338G>A		intron_variant		ENST00000233813.5
LOC124900515	XR_007088080.1	n.109+355G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGFBP5	ENST00000233813.5	c.337+3338G>A		intron_variant		1	NM_000599.4	P1
IGFBP5	ENST00000449583.1	c.337+3338G>A		intron_variant		3
IGFBP5	ENST00000486341.1	n.229+3338G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26450 AN: 151982 Hom.: 2483 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.0995

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.174 AC: 26463 AN: 152100 Hom.: 2482 Cov.: 32 AF XY: 0.168 AC XY: 12521 AN XY: 74342

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.0998

Gnomad4 FIN AF: 0.158

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.175

Alfa AF: 0.200 Hom.: 843

Bravo AF: 0.172

Asia WGS AF: 0.109 AC: 379 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	18
DANN	Benign	0.86

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: rs11575134; hg19: chr2-217555824;