12-102420554-C-G

Variant names:

• chr12-102420554-C-G
• rs5742678
• NM_000618.5:c.221-864G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000618.5(IGF1):​c.221-864G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.696 in 151,968 control chromosomes in the GnomAD database, including 37,135 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 0.70 (37135 hom., cov: 31)
• Consequence: IGF1 NM_000618.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.902
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF1	NM_000618.5	c.221-864G>C		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.221-864G>C		intron_variant	Intron 2 of 3	1	NM_000618.5	ENSP00000337612.7

Frequencies

GnomAD3 genomes AF: 0.697 AC: 105786 AN: 151850 Hom.: 37133 Cov.: 31

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.909

Gnomad AMR AF: 0.756

Gnomad ASJ AF: 0.736

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.690

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.732

Gnomad OTH AF: 0.700

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

GnomAD4 genome AF: 0.696 AC: 105819 AN: 151968 Hom.: 37135 Cov.: 31 AF XY: 0.695 AC XY: 51665 AN XY: 74298

African (AFR) AF: 0.636 AC: 26351 AN: 41406

American (AMR) AF: 0.756 AC: 11545 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.736 AC: 2554 AN: 3468

East Asian (EAS) AF: 0.556 AC: 2871 AN: 5166

South Asian (SAS) AF: 0.619 AC: 2983 AN: 4820

European-Finnish (FIN) AF: 0.690 AC: 7277 AN: 10552

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.732 AC: 49735 AN: 67966

Other (OTH) AF: 0.694 AC: 1463 AN: 2108

Alfa AF: 0.700 Hom.: 4416

Bravo AF: 0.699

Asia WGS AF: 0.566 AC: 1972 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.41
DANN	Benign	0.64
PhyloP100		-0.90
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: rs5742678; hg19: chr12-102814332;