chr12-102481086-A-G

Variant names:

• chr12-102481086-A-G
• rs5742612
• NM_001414005.1:c.-20+617T>C

Variant summary

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

The NM_001414005.1(IGF1):​c.-20+617T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0593 in 152,220 control chromosomes in the GnomAD database, including 522 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 0.059 (522 hom., cov: 32)
• Consequence: IGF1 NM_001414005.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.300
• Publications: 68 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 (EAS) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001414005.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF1	NM_001414005.1		c.-20+617T>C		intron	N/A	NP_001400934.1	P05019-1
	IGF1	NM_001414007.1		c.-20+617T>C		intron	N/A	NP_001400936.1	Q5U743

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF1	ENST00000644491.1		c.-20+617T>C		intron	N/A	ENSP00000494228.1	P05019-2
	IGF1	ENST00000906561.1		c.-388T>C		upstream_gene	N/A	ENSP00000576620.1
	IGF1	ENST00000906562.1		c.-215T>C		upstream_gene	N/A	ENSP00000576621.1

Frequencies

GnomAD3 genomes AF: 0.0592 AC: 9001 AN: 152102 Hom.: 516 Cov.: 32

Gnomad AFR AF: 0.0410

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.0873

Gnomad ASJ AF: 0.0196

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.0945

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0361

Gnomad OTH AF: 0.0621

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

GnomAD4 genome AF: 0.0593 AC: 9025 AN: 152220 Hom.: 522 Cov.: 32 AF XY: 0.0642 AC XY: 4778 AN XY: 74434

African (AFR) AF: 0.0409 AC: 1700 AN: 41540

American (AMR) AF: 0.0878 AC: 1341 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0196 AC: 68 AN: 3472

East Asian (EAS) AF: 0.305 AC: 1579 AN: 5172

South Asian (SAS) AF: 0.0946 AC: 456 AN: 4822

European-Finnish (FIN) AF: 0.112 AC: 1189 AN: 10602

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0361 AC: 2454 AN: 68012

Other (OTH) AF: 0.0681 AC: 144 AN: 2114

Alfa AF: 0.0435 Hom.: 694

Bravo AF: 0.0596

Asia WGS AF: 0.222 AC: 769 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	14
DANN	Benign	0.51
PhyloP100		0.30
PromoterAI		0.047	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs5742612; hg19: chr12-102874864;