12-102477481-C-T

Variant names:

• chr12-102477481-C-T
• rs2162679
• NM_000618.5:c.64-1682G>A

Variant summary

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

The NM_000618.5(IGF1):​c.64-1682G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 151,154 control chromosomes in the GnomAD database, including 43,105 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 0.74 (43105 hom., cov: 27)
• Consequence: IGF1 NM_000618.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94
• Publications: 39 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000618.5. 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_000618.5	MANE Select	c.64-1682G>A		intron	N/A	NP_000609.1	Q5U743
	IGF1	NM_001111285.3		c.64-1682G>A		intron	N/A	NP_001104755.1	P05019-1
	IGF1	NM_001414005.1		c.64-1682G>A		intron	N/A	NP_001400934.1	P05019-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF1	ENST00000337514.11	TSL:1 MANE Select	c.64-1682G>A		intron	N/A	ENSP00000337612.7	P05019-2
	IGF1	ENST00000307046.8	TSL:1	c.64-1682G>A		intron	N/A	ENSP00000302665.8	P05019-1
	IGF1	ENST00000424202.6	TSL:1	c.15+1006G>A		intron	N/A	ENSP00000416811.2	P05019-3

Frequencies

GnomAD3 genomes AF: 0.745 AC: 112498 AN: 151044 Hom.: 43104 Cov.: 27

Gnomad AFR AF: 0.551

Gnomad AMI AF: 0.801

Gnomad AMR AF: 0.787

Gnomad ASJ AF: 0.786

Gnomad EAS AF: 0.637

Gnomad SAS AF: 0.747

Gnomad FIN AF: 0.813

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.846

Gnomad OTH AF: 0.772

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

GnomAD4 genome AF: 0.745 AC: 112542 AN: 151154 Hom.: 43105 Cov.: 27 AF XY: 0.744 AC XY: 54840 AN XY: 73722

African (AFR) AF: 0.551 AC: 22676 AN: 41142

American (AMR) AF: 0.787 AC: 11947 AN: 15188

Ashkenazi Jewish (ASJ) AF: 0.786 AC: 2726 AN: 3468

East Asian (EAS) AF: 0.637 AC: 3271 AN: 5132

South Asian (SAS) AF: 0.747 AC: 3572 AN: 4784

European-Finnish (FIN) AF: 0.813 AC: 8335 AN: 10258

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.846 AC: 57436 AN: 67884

Other (OTH) AF: 0.768 AC: 1609 AN: 2096

Alfa AF: 0.817 Hom.: 88941

Bravo AF: 0.730

Asia WGS AF: 0.681 AC: 2368 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.20
DANN	Benign	0.38
PhyloP100		-1.9
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: rs2162679; hg19: chr12-102871259;