12-102470201-A-T

Variant names:

• chr12-102470201-A-T
• rs17882461
• NM_000618.5:c.220+5442T>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_000618.5(IGF1):​c.220+5442T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,124 control chromosomes in the GnomAD database, including 3,168 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 0.20 (3168 hom., cov: 32)
• Consequence: IGF1 NM_000618.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.41
• Publications: 1 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.21).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.222 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.220+5442T>A		intron	N/A	NP_000609.1	Q5U743
	IGF1	NM_001111285.3		c.220+5442T>A		intron	N/A	NP_001104755.1	P05019-1
	IGF1	NM_001414005.1		c.220+5442T>A		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.220+5442T>A		intron	N/A	ENSP00000337612.7	P05019-2
	IGF1	ENST00000307046.8	TSL:1	c.220+5442T>A		intron	N/A	ENSP00000302665.8	P05019-1
	IGF1	ENST00000424202.6	TSL:1	c.172+5442T>A		intron	N/A	ENSP00000416811.2	P05019-3

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30472 AN: 152006 Hom.: 3165 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.200 AC: 30494 AN: 152124 Hom.: 3168 Cov.: 32 AF XY: 0.199 AC XY: 14824 AN XY: 74358

African (AFR) AF: 0.182 AC: 7544 AN: 41512

American (AMR) AF: 0.125 AC: 1916 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 692 AN: 3470

East Asian (EAS) AF: 0.160 AC: 826 AN: 5166

South Asian (SAS) AF: 0.197 AC: 951 AN: 4820

European-Finnish (FIN) AF: 0.259 AC: 2742 AN: 10578

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.225 AC: 15296 AN: 67990

Other (OTH) AF: 0.187 AC: 395 AN: 2110

Alfa AF: 0.218 Hom.: 478

Bravo AF: 0.188

Asia WGS AF: 0.184 AC: 639 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.21
CADD	Benign	17
DANN	Benign	0.87
PhyloP100		2.4
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: rs17882461; hg19: chr12-102863979;