chr12-102456445-A-G

Variant names:

• chr12-102456445-A-G
• rs9989002
• NM_000618.5:c.220+19198T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_000618.5(IGF1):​c.220+19198T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.749 in 152,064 control chromosomes in the GnomAD database, including 42,806 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 (42806 hom., cov: 31)
• Consequence: IGF1 NM_000618.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0250
• Publications: 16 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.82 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.220+19198T>C		intron	N/A	NP_000609.1	Q5U743
	IGF1	NM_001111285.3		c.220+19198T>C		intron	N/A	NP_001104755.1	P05019-1
	IGF1	NM_001414005.1		c.220+19198T>C		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.220+19198T>C		intron	N/A	ENSP00000337612.7	P05019-2
	IGF1	ENST00000307046.8	TSL:1	c.220+19198T>C		intron	N/A	ENSP00000302665.8	P05019-1
	IGF1	ENST00000424202.6	TSL:1	c.172+19198T>C		intron	N/A	ENSP00000416811.2	P05019-3

Frequencies

GnomAD3 genomes AF: 0.749 AC: 113829 AN: 151946 Hom.: 42769 Cov.: 31

Gnomad AFR AF: 0.762

Gnomad AMI AF: 0.904

Gnomad AMR AF: 0.832

Gnomad ASJ AF: 0.742

Gnomad EAS AF: 0.839

Gnomad SAS AF: 0.732

Gnomad FIN AF: 0.716

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.720

Gnomad OTH AF: 0.768

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

GnomAD4 genome AF: 0.749 AC: 113918 AN: 152064 Hom.: 42806 Cov.: 31 AF XY: 0.752 AC XY: 55901 AN XY: 74346

African (AFR) AF: 0.762 AC: 31601 AN: 41462

American (AMR) AF: 0.833 AC: 12733 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.742 AC: 2576 AN: 3470

East Asian (EAS) AF: 0.839 AC: 4348 AN: 5182

South Asian (SAS) AF: 0.731 AC: 3513 AN: 4806

European-Finnish (FIN) AF: 0.716 AC: 7549 AN: 10546

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.720 AC: 48934 AN: 67984

Other (OTH) AF: 0.768 AC: 1623 AN: 2114

Alfa AF: 0.726 Hom.: 6002

Bravo AF: 0.762

Asia WGS AF: 0.786 AC: 2731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	15
DANN	Benign	0.77
PhyloP100		-0.025
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs9989002; hg19: chr12-102850223;