12-102402744-G-T

Variant names:

• chr12-102402744-G-T
• rs1520220
• NM_000618.5:c.403-178C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000618.5(IGF1):​c.403-178C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000636 in 471,802 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000064 (0 hom.)
• Consequence: IGF1 NM_000618.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.419
• Publications: 73 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)

HELLPAR (HGNC:43984): (HELLP associated long non-coding RNA)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

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.403-178C>A		intron	N/A	NP_000609.1	Q5U743
	IGF1	NM_001111283.3		c.452-178C>A		intron	N/A	NP_001104753.1	P05019-4
	IGF1	NM_001414007.1		c.403-178C>A		intron	N/A	NP_001400936.1	Q5U743

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF1	ENST00000337514.11	TSL:1 MANE Select	c.403-178C>A		intron	N/A	ENSP00000337612.7	P05019-2
	IGF1	ENST00000424202.6	TSL:1	c.355-178C>A		intron	N/A	ENSP00000416811.2	P05019-3
	IGF1	ENST00000392904.5	TSL:5	c.452-178C>A		intron	N/A	ENSP00000376637.1	P05019-4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000636 AC: 3 AN: 471802 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 252250

African (AFR) AF: 0.00 AC: 0 AN: 13470

American (AMR) AF: 0.00 AC: 0 AN: 27016

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15142

East Asian (EAS) AF: 0.00 AC: 0 AN: 30416

South Asian (SAS) AF: 0.00 AC: 0 AN: 50298

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30938

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2026

European-Non Finnish (NFE) AF: 0.0000109 AC: 3 AN: 275812

Other (OTH) AF: 0.00 AC: 0 AN: 26684

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 2644

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.1
DANN	Benign	0.45
PhyloP100		0.42

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: rs1520220; hg19: chr12-102796522;