rs17796225

Variant names:

• chr12-102472860-T-C
• rs17796225
• NM_000618.5:c.220+2783A>G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF1	NM_000618.5	c.220+2783A>G		intron_variant	Intron 2 of 3	ENST00000337514.11	NP_000609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGF1	ENST00000337514.11	c.220+2783A>G		intron_variant	Intron 2 of 3	1	NM_000618.5	ENSP00000337612.7

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

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.161

Gnomad4 ASJ AF: 0.225

Gnomad4 EAS AF: 0.161

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.298

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.223

Alfa AF: 0.248 Hom.: 4953

Bravo AF: 0.237

Asia WGS AF: 0.191 AC: 662 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	9.6
DANN	Benign	0.91

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

Publications

LitVar

Other links and lift over

dbSNP: rs17796225; hg19: chr12-102866638;