rs11575134

Variant names:

• chr2-216691101-C-T
• rs11575134
• NM_000599.4:c.337+3338G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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 -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.

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+3338G>A		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+3338G>A		intron	N/A	ENSP00000233813.4
	IGFBP5	ENST00000449583.1	TSL:3	c.337+3338G>A		intron	N/A	ENSP00000413474.1
	IGFBP5	ENST00000486341.1	TSL:2	n.229+3338G>A		intron	N/A

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

African (AFR) AF: 0.125 AC: 5176 AN: 41476

American (AMR) AF: 0.153 AC: 2337 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 723 AN: 3472

East Asian (EAS) AF: 0.125 AC: 648 AN: 5164

South Asian (SAS) AF: 0.0998 AC: 481 AN: 4818

European-Finnish (FIN) AF: 0.158 AC: 1674 AN: 10590

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14772 AN: 67972

Other (OTH) AF: 0.175 AC: 371 AN: 2116

Alfa AF: 0.206 Hom.: 1529

Bravo AF: 0.172

Asia WGS AF: 0.109 AC: 379 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	18
DANN	Benign	0.86
PhyloP100		0.33
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: rs11575134; hg19: chr2-217555824;