12-102475707-C-G

Variant names:

• chr12-102475707-C-G
• rs3729846
• NM_000618.5:c.156G>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001111285.3(IGF1):​c.156G>C​(p.Thr52Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T52T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IGF1 NM_001111285.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75
• Publications: 2 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP7: Synonymous conserved (PhyloP=-1.75 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001111285.3. 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.156G>C	p.Thr52Thr	synonymous	Exon 2 of 4	NP_000609.1
	IGF1	NM_001111285.3		c.156G>C	p.Thr52Thr	synonymous	Exon 2 of 4	NP_001104755.1
	IGF1	NM_001414005.1		c.156G>C	p.Thr52Thr	synonymous	Exon 3 of 5	NP_001400934.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF1	ENST00000337514.11	TSL:1 MANE Select	c.156G>C	p.Thr52Thr	synonymous	Exon 2 of 4	ENSP00000337612.7
	IGF1	ENST00000307046.8	TSL:1	c.156G>C	p.Thr52Thr	synonymous	Exon 2 of 4	ENSP00000302665.8
	IGF1	ENST00000424202.6	TSL:1	c.108G>C	p.Thr36Thr	synonymous	Exon 2 of 4	ENSP00000416811.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.54
DANN	Benign	0.59
PhyloP100		-1.8

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: rs3729846; hg19: chr12-102869485;