12-102445218-A-G

Variant names:

• chr12-102445218-A-G
• rs10778174
• NM_000618.5:c.221-25528T>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.221-25528T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.764 in 151,856 control chromosomes in the GnomAD database, including 44,486 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 0.76 (44486 hom., cov: 31)
• Consequence: IGF1 NM_000618.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• Publications: 3 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=-1.04).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF1	NM_000618.5	c.221-25528T>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.221-25528T>C		intron_variant	Intron 2 of 3	1	NM_000618.5	ENSP00000337612.7

Frequencies

GnomAD3 genomes AF: 0.764 AC: 115943 AN: 151738 Hom.: 44453 Cov.: 31

Gnomad AFR AF: 0.766

Gnomad AMI AF: 0.909

Gnomad AMR AF: 0.834

Gnomad ASJ AF: 0.739

Gnomad EAS AF: 0.830

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.768

Gnomad MID AF: 0.717

Gnomad NFE AF: 0.746

Gnomad OTH AF: 0.771

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

GnomAD4 genome AF: 0.764 AC: 116030 AN: 151856 Hom.: 44486 Cov.: 31 AF XY: 0.766 AC XY: 56850 AN XY: 74200

African (AFR) AF: 0.766 AC: 31777 AN: 41480

American (AMR) AF: 0.834 AC: 12737 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.739 AC: 2542 AN: 3438

East Asian (EAS) AF: 0.830 AC: 4294 AN: 5172

South Asian (SAS) AF: 0.696 AC: 3334 AN: 4788

European-Finnish (FIN) AF: 0.768 AC: 8083 AN: 10526

Middle Eastern (MID) AF: 0.712 AC: 208 AN: 292

European-Non Finnish (NFE) AF: 0.746 AC: 50601 AN: 67866

Other (OTH) AF: 0.770 AC: 1625 AN: 2110

Alfa AF: 0.675 Hom.: 2132

Bravo AF: 0.774

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.42
PhyloP100		-1.5
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: rs10778174; hg19: chr12-102838996;