rs17882264

Variant names:

• chr12-102477578-T-C
• rs17882264
• NM_000618.5:c.64-1779A>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.64-1779A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0578 in 150,604 control chromosomes in the GnomAD database, including 333 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 0.058 (333 hom., cov: 29)
• Consequence: IGF1 NM_000618.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.444
• Publications: 0 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0861 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF1	NM_000618.5	c.64-1779A>G		intron_variant	Intron 1 of 3	ENST00000337514.11	NP_000609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGF1	ENST00000337514.11	c.64-1779A>G		intron_variant	Intron 1 of 3	1	NM_000618.5	ENSP00000337612.7

Frequencies

GnomAD3 genomes AF: 0.0578 AC: 8701 AN: 150496 Hom.: 332 Cov.: 29

Gnomad AFR AF: 0.0159

Gnomad AMI AF: 0.0374

Gnomad AMR AF: 0.0448

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0376

Gnomad FIN AF: 0.0592

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0879

Gnomad OTH AF: 0.0596

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

GnomAD4 genome AF: 0.0578 AC: 8700 AN: 150604 Hom.: 333 Cov.: 29 AF XY: 0.0544 AC XY: 3992 AN XY: 73360

African (AFR) AF: 0.0159 AC: 654 AN: 41236

American (AMR) AF: 0.0448 AC: 671 AN: 14984

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 464 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5136

South Asian (SAS) AF: 0.0372 AC: 176 AN: 4728

European-Finnish (FIN) AF: 0.0592 AC: 597 AN: 10086

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0880 AC: 5954 AN: 67690

Other (OTH) AF: 0.0591 AC: 123 AN: 2082

Alfa AF: 0.0723 Hom.: 80

Bravo AF: 0.0572

Asia WGS AF: 0.0160 AC: 56 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	12
DANN	Benign	0.66
PhyloP100		0.44
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: rs17882264; hg19: chr12-102871356;