12-102402744-G-C

Variant names:

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

Variant summary

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

The NM_000618.5(IGF1):​c.403-178C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.771 in 623,316 control chromosomes in the GnomAD database, including 187,764 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 0.75 (43833 hom., cov: 31)
  • Exomes 𝑓: 0.78 (143931 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.814 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.403-178C>G		intron	N/A	NP_000609.1	Q5U743
	IGF1	NM_001111283.3		c.452-178C>G		intron	N/A	NP_001104753.1	P05019-4
	IGF1	NM_001414007.1		c.403-178C>G		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>G		intron	N/A	ENSP00000337612.7	P05019-2
	IGF1	ENST00000424202.6	TSL:1	c.355-178C>G		intron	N/A	ENSP00000416811.2	P05019-3
	IGF1	ENST00000392904.5	TSL:5	c.452-178C>G		intron	N/A	ENSP00000376637.1	P05019-4

Frequencies

GnomAD3 genomes AF: 0.754 AC: 114609 AN: 151940 Hom.: 43833 Cov.: 31

Gnomad AFR AF: 0.640

Gnomad AMI AF: 0.947

Gnomad AMR AF: 0.794

Gnomad ASJ AF: 0.752

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.694

Gnomad FIN AF: 0.832

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.819

Gnomad OTH AF: 0.759

GnomAD4 exome AF: 0.776 AC: 365773 AN: 471258 Hom.: 143931 AF XY: 0.773 AC XY: 194808 AN XY: 251966

African (AFR) AF: 0.644 AC: 8662 AN: 13452

American (AMR) AF: 0.772 AC: 20825 AN: 26982

Ashkenazi Jewish (ASJ) AF: 0.745 AC: 11264 AN: 15122

East Asian (EAS) AF: 0.537 AC: 16298 AN: 30362

South Asian (SAS) AF: 0.713 AC: 35822 AN: 50260

European-Finnish (FIN) AF: 0.820 AC: 25354 AN: 30910

Middle Eastern (MID) AF: 0.716 AC: 1450 AN: 2026

European-Non Finnish (NFE) AF: 0.819 AC: 225730 AN: 275508

Other (OTH) AF: 0.765 AC: 20368 AN: 26636

GnomAD4 genome AF: 0.754 AC: 114637 AN: 152058 Hom.: 43833 Cov.: 31 AF XY: 0.754 AC XY: 56079 AN XY: 74344

African (AFR) AF: 0.640 AC: 26514 AN: 41444

American (AMR) AF: 0.793 AC: 12119 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.752 AC: 2608 AN: 3466

East Asian (EAS) AF: 0.557 AC: 2878 AN: 5166

South Asian (SAS) AF: 0.692 AC: 3336 AN: 4818

European-Finnish (FIN) AF: 0.832 AC: 8812 AN: 10594

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.819 AC: 55692 AN: 67974

Other (OTH) AF: 0.752 AC: 1589 AN: 2112

Alfa AF: 0.738 Hom.: 2644

Bravo AF: 0.743

Asia WGS AF: 0.590 AC: 2053 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.2
DANN	Benign	0.40
PhyloP100		0.42
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: rs1520220; hg19: chr12-102796522;