chr12-102450458-G-A

Variant names:

• chr12-102450458-G-A
• rs10735380
• NM_000618.5:c.220+25185C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000618.5(IGF1):​c.220+25185C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.762 in 152,178 control chromosomes in the GnomAD database, including 44,285 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 0.76 (44285 hom., cov: 33)
• Consequence: IGF1 NM_000618.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.335
• Publications: 31 publications found

Genes affected

IGF1 (HGNC:5464): (insulin like growth factor 1) The protein encoded by this gene is similar to insulin in function and structure and is a member of a family of proteins involved in mediating growth and development. The encoded protein is processed from a precursor, bound by a specific receptor, and secreted. Defects in this gene are a cause of insulin-like growth factor I deficiency. Alternative splicing results in multiple transcript variants encoding different isoforms that may undergo similar processing to generate mature protein. [provided by RefSeq, Sep 2015]

LINC02456 (HGNC:53389): (long intergenic non-protein coding RNA 2456)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF1	NM_000618.5	c.220+25185C>T		intron_variant	Intron 2 of 3	ENST00000337514.11	NP_000609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGF1	ENST00000337514.11	c.220+25185C>T		intron_variant	Intron 2 of 3	1	NM_000618.5	ENSP00000337612.7

Frequencies

GnomAD3 genomes AF: 0.761 AC: 115792 AN: 152060 Hom.: 44246 Cov.: 33

Gnomad AFR AF: 0.808

Gnomad AMI AF: 0.908

Gnomad AMR AF: 0.833

Gnomad ASJ AF: 0.734

Gnomad EAS AF: 0.829

Gnomad SAS AF: 0.702

Gnomad FIN AF: 0.720

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.722

Gnomad OTH AF: 0.766

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

GnomAD4 genome AF: 0.762 AC: 115886 AN: 152178 Hom.: 44285 Cov.: 33 AF XY: 0.763 AC XY: 56762 AN XY: 74396

African (AFR) AF: 0.808 AC: 33583 AN: 41544

American (AMR) AF: 0.833 AC: 12734 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.734 AC: 2547 AN: 3470

East Asian (EAS) AF: 0.829 AC: 4290 AN: 5172

South Asian (SAS) AF: 0.701 AC: 3374 AN: 4816

European-Finnish (FIN) AF: 0.720 AC: 7614 AN: 10578

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.722 AC: 49087 AN: 67984

Other (OTH) AF: 0.765 AC: 1619 AN: 2116

Alfa AF: 0.725 Hom.: 19941

Bravo AF: 0.776

Asia WGS AF: 0.774 AC: 2690 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.3
DANN	Benign	0.54
PhyloP100		-0.34
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: rs10735380; hg19: chr12-102844236;