12-102465050-G-C

Variant names:

• chr12-102465050-G-C
• rs12423791
• NM_000618.5:c.220+10593C>G

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+10593C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0321 in 152,294 control chromosomes in the GnomAD database, including 304 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 0.032 (304 hom., cov: 32)
• Consequence: IGF1 NM_000618.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.102
• Publications: 20 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF1	NM_000618.5	c.220+10593C>G		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+10593C>G		intron_variant	Intron 2 of 3	1	NM_000618.5	ENSP00000337612.7

Frequencies

GnomAD3 genomes AF: 0.0321 AC: 4882 AN: 152176 Hom.: 302 Cov.: 32

Gnomad AFR AF: 0.00601

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0662

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.0843

Gnomad FIN AF: 0.0757

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0132

Gnomad OTH AF: 0.0382

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

GnomAD4 genome AF: 0.0321 AC: 4890 AN: 152294 Hom.: 304 Cov.: 32 AF XY: 0.0367 AC XY: 2736 AN XY: 74466

African (AFR) AF: 0.00599 AC: 249 AN: 41576

American (AMR) AF: 0.0668 AC: 1021 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00403 AC: 14 AN: 3470

East Asian (EAS) AF: 0.273 AC: 1415 AN: 5174

South Asian (SAS) AF: 0.0843 AC: 407 AN: 4826

European-Finnish (FIN) AF: 0.0757 AC: 802 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0132 AC: 900 AN: 68038

Other (OTH) AF: 0.0388 AC: 82 AN: 2116

Alfa AF: 0.0222 Hom.: 19

Bravo AF: 0.0328

Asia WGS AF: 0.195 AC: 676 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.64
PhyloP100		0.10
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: rs12423791; hg19: chr12-102858828;