chr12-102417461-A-G

Variant names:

• chr12-102417461-A-G
• rs11111267
• NM_000618.5:c.402+2048T>C

Variant summary

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

The NM_000618.5(IGF1):​c.402+2048T>C variant causes a intron change. The variant allele was found at a frequency of 0.166 in 782,022 control chromosomes in the GnomAD database, including 11,450 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 0.14 (1775 hom., cov: 32)
  • Exomes 𝑓: 0.17 (9675 hom.)
• Consequence: IGF1 NM_000618.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.50
• Publications: 3 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=-0.72).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF1	NM_000618.5	c.402+2048T>C		intron_variant	Intron 3 of 3	ENST00000337514.11	NP_000609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGF1	ENST00000337514.11	c.402+2048T>C		intron_variant	Intron 3 of 3	1	NM_000618.5	ENSP00000337612.7

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21324 AN: 152134 Hom.: 1773 Cov.: 32

Gnomad AFR AF: 0.0595

Gnomad AMI AF: 0.0725

Gnomad AMR AF: 0.0943

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.142

GnomAD4 exome AF: 0.172 AC: 108404 AN: 629768 Hom.: 9675 Cov.: 8 AF XY: 0.172 AC XY: 50944 AN XY: 296094

African (AFR) AF: 0.0500 AC: 608 AN: 12166

American (AMR) AF: 0.0740 AC: 97 AN: 1310

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 738 AN: 4706

East Asian (EAS) AF: 0.177 AC: 697 AN: 3932

South Asian (SAS) AF: 0.172 AC: 2165 AN: 12588

European-Finnish (FIN) AF: 0.207 AC: 252 AN: 1218

Middle Eastern (MID) AF: 0.182 AC: 231 AN: 1266

European-Non Finnish (NFE) AF: 0.175 AC: 99841 AN: 571154

Other (OTH) AF: 0.176 AC: 3775 AN: 21428

GnomAD4 genome AF: 0.140 AC: 21334 AN: 152254 Hom.: 1775 Cov.: 32 AF XY: 0.140 AC XY: 10423 AN XY: 74430

African (AFR) AF: 0.0595 AC: 2471 AN: 41564

American (AMR) AF: 0.0942 AC: 1442 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 543 AN: 3470

East Asian (EAS) AF: 0.167 AC: 867 AN: 5178

South Asian (SAS) AF: 0.180 AC: 868 AN: 4822

European-Finnish (FIN) AF: 0.205 AC: 2172 AN: 10584

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12557 AN: 68012

Other (OTH) AF: 0.143 AC: 303 AN: 2114

Alfa AF: 0.164 Hom.: 388

Bravo AF: 0.126

Asia WGS AF: 0.172 AC: 598 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	14
DANN	Benign	0.85
PhyloP100		4.5
Mutation Taster		=99/1	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: rs11111267; hg19: chr12-102811239;