rs12313279

Variant names:

• chr12-102452726-A-G
• rs12313279
• NM_000618.5:c.220+22917T>C

Your query was ambiguous. Multiple possible variants found:

• chr12-102452726-A-G
• chr12-102452726-A-T

Variant summary

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

The NM_000618.5(IGF1):​c.220+22917T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.679 in 152,050 control chromosomes in the GnomAD database, including 35,328 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 0.68 (35328 hom., cov: 32)
• Consequence: IGF1 NM_000618.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.129
• Publications: 4 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF1	NM_000618.5	c.220+22917T>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.220+22917T>C		intron_variant	Intron 2 of 3	1	NM_000618.5	ENSP00000337612.7

Frequencies

GnomAD3 genomes AF: 0.680 AC: 103267 AN: 151932 Hom.: 35327 Cov.: 32

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.904

Gnomad AMR AF: 0.750

Gnomad ASJ AF: 0.730

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.652

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.705

Gnomad OTH AF: 0.689

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

GnomAD4 genome AF: 0.679 AC: 103299 AN: 152050 Hom.: 35328 Cov.: 32 AF XY: 0.679 AC XY: 50471 AN XY: 74322

African (AFR) AF: 0.630 AC: 26132 AN: 41452

American (AMR) AF: 0.750 AC: 11458 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.730 AC: 2534 AN: 3472

East Asian (EAS) AF: 0.556 AC: 2878 AN: 5172

South Asian (SAS) AF: 0.651 AC: 3137 AN: 4820

European-Finnish (FIN) AF: 0.638 AC: 6731 AN: 10552

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.705 AC: 47951 AN: 67986

Other (OTH) AF: 0.683 AC: 1443 AN: 2112

Alfa AF: 0.655 Hom.: 5195

Bravo AF: 0.685

Asia WGS AF: 0.573 AC: 1994 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.4
DANN	Benign	0.69
PhyloP100		-0.13
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: rs12313279; hg19: chr12-102846504;