12-102415852-G-C

Variant names:

• chr12-102415852-G-C
• rs17727841
• NM_000618.5:c.402+3657C>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.402+3657C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,126 control chromosomes in the GnomAD database, including 1,708 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 0.13 (1708 hom., cov: 31)
  • Exomes 𝑓: 0.080 (0 hom.)
• Consequence: IGF1 NM_000618.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.301
• Publications: 20 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.182 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF1	NM_000618.5	MANE Select	c.402+3657C>G		intron	N/A	NP_000609.1
	IGF1	NM_001111283.3		c.451+2103C>G		intron	N/A	NP_001104753.1
	IGF1	NM_001414007.1		c.402+3657C>G		intron	N/A	NP_001400936.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF1	ENST00000337514.11	TSL:1 MANE Select	c.402+3657C>G		intron	N/A	ENSP00000337612.7
	IGF1	ENST00000424202.6	TSL:1	c.354+3657C>G		intron	N/A	ENSP00000416811.2
	IGF1	ENST00000392904.5	TSL:5	c.451+2103C>G		intron	N/A	ENSP00000376637.1

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20086 AN: 151896 Hom.: 1707 Cov.: 31

Gnomad AFR AF: 0.0331

Gnomad AMI AF: 0.0725

Gnomad AMR AF: 0.0920

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.153

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.135

GnomAD4 exome AF: 0.0804 AC: 9 AN: 112 Hom.: 0 AF XY: 0.0833 AC XY: 8 AN XY: 96

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.0682 AC: 6 AN: 88

Other (OTH) AF: 0.100 AC: 1 AN: 10

GnomAD4 genome AF: 0.132 AC: 20086 AN: 152014 Hom.: 1708 Cov.: 31 AF XY: 0.132 AC XY: 9836 AN XY: 74294

African (AFR) AF: 0.0331 AC: 1372 AN: 41508

American (AMR) AF: 0.0919 AC: 1404 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 543 AN: 3470

East Asian (EAS) AF: 0.167 AC: 858 AN: 5144

South Asian (SAS) AF: 0.169 AC: 813 AN: 4806

European-Finnish (FIN) AF: 0.205 AC: 2165 AN: 10546

Middle Eastern (MID) AF: 0.154 AC: 45 AN: 292

European-Non Finnish (NFE) AF: 0.184 AC: 12535 AN: 67956

Other (OTH) AF: 0.135 AC: 285 AN: 2108

Alfa AF: 0.161 Hom.: 307

Bravo AF: 0.118

Asia WGS AF: 0.147 AC: 509 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.68
PhyloP100		-0.30
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: rs17727841; hg19: chr12-102809630;