rs2288378

Variant names:

• chr12-102436230-T-C
• rs2288378
• NM_000618.5:c.221-16540A>G

Your query was ambiguous. Multiple possible variants found:

• chr12-102436230-T-C
• chr12-102436230-T-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.221-16540A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 152,118 control chromosomes in the GnomAD database, including 44,633 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 0.77 (44633 hom., cov: 32)
• Consequence: IGF1 NM_000618.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0320
• Publications: 17 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=-0.76).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF1	NM_000618.5	c.221-16540A>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.221-16540A>G		intron_variant	Intron 2 of 3	1	NM_000618.5	ENSP00000337612.7

Frequencies

GnomAD3 genomes AF: 0.765 AC: 116354 AN: 152000 Hom.: 44596 Cov.: 32

Gnomad AFR AF: 0.767

Gnomad AMI AF: 0.909

Gnomad AMR AF: 0.835

Gnomad ASJ AF: 0.741

Gnomad EAS AF: 0.830

Gnomad SAS AF: 0.712

Gnomad FIN AF: 0.768

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.747

Gnomad OTH AF: 0.773

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

GnomAD4 genome AF: 0.765 AC: 116444 AN: 152118 Hom.: 44633 Cov.: 32 AF XY: 0.768 AC XY: 57073 AN XY: 74348

African (AFR) AF: 0.768 AC: 31841 AN: 41480

American (AMR) AF: 0.835 AC: 12763 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.741 AC: 2571 AN: 3470

East Asian (EAS) AF: 0.830 AC: 4296 AN: 5176

South Asian (SAS) AF: 0.711 AC: 3419 AN: 4812

European-Finnish (FIN) AF: 0.768 AC: 8130 AN: 10586

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

European-Non Finnish (NFE) AF: 0.746 AC: 50754 AN: 67990

Other (OTH) AF: 0.772 AC: 1628 AN: 2110

Alfa AF: 0.746 Hom.: 21854

Bravo AF: 0.774

Asia WGS AF: 0.777 AC: 2703 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	13
DANN	Benign	0.71
PhyloP100		0.032
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: rs2288378; hg19: chr12-102830008;