rs2373722

Variant names:

• chr12-102446679-A-G
• rs2373722
• NM_000618.5:c.221-26989T>C

Your query was ambiguous. Multiple possible variants found:

• chr12-102446679-A-G
• chr12-102446679-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.221-26989T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.942 in 152,254 control chromosomes in the GnomAD database, including 67,670 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 0.94 (67670 hom., cov: 31)
• Consequence: IGF1 NM_000618.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 15 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=-1.05).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000618.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF1	NM_000618.5	MANE Select	c.221-26989T>C		intron	N/A	NP_000609.1	Q5U743
	IGF1	NM_001111285.3		c.221-26989T>C		intron	N/A	NP_001104755.1	P05019-1
	IGF1	NM_001414005.1		c.221-26989T>C		intron	N/A	NP_001400934.1	P05019-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF1	ENST00000337514.11	TSL:1 MANE Select	c.221-26989T>C		intron	N/A	ENSP00000337612.7	P05019-2
	IGF1	ENST00000307046.8	TSL:1	c.221-26989T>C		intron	N/A	ENSP00000302665.8	P05019-1
	IGF1	ENST00000424202.6	TSL:1	c.173-26989T>C		intron	N/A	ENSP00000416811.2	P05019-3

Frequencies

GnomAD3 genomes AF: 0.942 AC: 143384 AN: 152136 Hom.: 67617 Cov.: 31

Gnomad AFR AF: 0.954

Gnomad AMI AF: 0.981

Gnomad AMR AF: 0.943

Gnomad ASJ AF: 0.898

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.898

Gnomad FIN AF: 0.975

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.932

Gnomad OTH AF: 0.932

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

GnomAD4 genome AF: 0.942 AC: 143496 AN: 152254 Hom.: 67670 Cov.: 31 AF XY: 0.944 AC XY: 70291 AN XY: 74458

African (AFR) AF: 0.954 AC: 39622 AN: 41544

American (AMR) AF: 0.943 AC: 14427 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.898 AC: 3115 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5181 AN: 5188

South Asian (SAS) AF: 0.897 AC: 4331 AN: 4830

European-Finnish (FIN) AF: 0.975 AC: 10318 AN: 10586

Middle Eastern (MID) AF: 0.878 AC: 258 AN: 294

European-Non Finnish (NFE) AF: 0.932 AC: 63381 AN: 68020

Other (OTH) AF: 0.932 AC: 1968 AN: 2112

Alfa AF: 0.934 Hom.: 7731

Bravo AF: 0.942

Asia WGS AF: 0.958 AC: 3329 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.9
DANN	Benign	0.15
PhyloP100		-1.1
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: rs2373722; hg19: chr12-102840457;