rs17796225

Variant names:

• chr12-102472860-T-C
• rs17796225
• NM_000618.5:c.220+2783A>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.220+2783A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 151,952 control chromosomes in the GnomAD database, including 4,764 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 0.25 (4764 hom., cov: 32)
• Consequence: IGF1 NM_000618.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.190
• Publications: 9 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=-0.64).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.264 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.220+2783A>G		intron	N/A	NP_000609.1
	IGF1	NM_001111285.3		c.220+2783A>G		intron	N/A	NP_001104755.1
	IGF1	NM_001414005.1		c.220+2783A>G		intron	N/A	NP_001400934.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF1	ENST00000337514.11	TSL:1 MANE Select	c.220+2783A>G		intron	N/A	ENSP00000337612.7
	IGF1	ENST00000307046.8	TSL:1	c.220+2783A>G		intron	N/A	ENSP00000302665.8
	IGF1	ENST00000424202.6	TSL:1	c.172+2783A>G		intron	N/A	ENSP00000416811.2

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37610 AN: 151834 Hom.: 4757 Cov.: 32

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.223

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

GnomAD4 genome AF: 0.248 AC: 37650 AN: 151952 Hom.: 4764 Cov.: 32 AF XY: 0.246 AC XY: 18259 AN XY: 74280

African (AFR) AF: 0.268 AC: 11112 AN: 41416

American (AMR) AF: 0.161 AC: 2453 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 779 AN: 3466

East Asian (EAS) AF: 0.161 AC: 832 AN: 5160

South Asian (SAS) AF: 0.199 AC: 956 AN: 4806

European-Finnish (FIN) AF: 0.298 AC: 3154 AN: 10570

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17632 AN: 67944

Other (OTH) AF: 0.223 AC: 471 AN: 2112

Alfa AF: 0.249 Hom.: 7232

Bravo AF: 0.237

Asia WGS AF: 0.191 AC: 662 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	9.6
DANN	Benign	0.91
PhyloP100		-0.19
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: rs17796225; hg19: chr12-102866638;