12-102405820-A-G

Variant names:

• chr12-102405820-A-G
• rs5742692
• NM_000618.5:c.403-3254T>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.403-3254T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0671 in 152,332 control chromosomes in the GnomAD database, including 696 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 0.067 (696 hom., cov: 32)
• Consequence: IGF1 NM_000618.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.104
• Publications: 24 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.261 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF1	NM_000618.5	MANE Select	c.403-3254T>C		intron	N/A	NP_000609.1
	IGF1	NM_001111283.3		c.452-3254T>C		intron	N/A	NP_001104753.1
	IGF1	NM_001414007.1		c.403-3254T>C		intron	N/A	NP_001400936.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF1	ENST00000337514.11	TSL:1 MANE Select	c.403-3254T>C		intron	N/A	ENSP00000337612.7
	IGF1	ENST00000424202.6	TSL:1	c.355-3254T>C		intron	N/A	ENSP00000416811.2
	IGF1	ENST00000392904.5	TSL:5	c.452-3254T>C		intron	N/A	ENSP00000376637.1

Frequencies

GnomAD3 genomes AF: 0.0668 AC: 10169 AN: 152214 Hom.: 681 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0770

Gnomad ASJ AF: 0.00374

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.0593

Gnomad FIN AF: 0.0792

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0145

Gnomad OTH AF: 0.0678

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

GnomAD4 genome AF: 0.0671 AC: 10226 AN: 152332 Hom.: 696 Cov.: 32 AF XY: 0.0699 AC XY: 5208 AN XY: 74492

African (AFR) AF: 0.128 AC: 5335 AN: 41564

American (AMR) AF: 0.0776 AC: 1188 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00374 AC: 13 AN: 3472

East Asian (EAS) AF: 0.273 AC: 1415 AN: 5178

South Asian (SAS) AF: 0.0594 AC: 287 AN: 4832

European-Finnish (FIN) AF: 0.0792 AC: 842 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0146 AC: 990 AN: 68038

Other (OTH) AF: 0.0733 AC: 155 AN: 2116

Alfa AF: 0.0344 Hom.: 1271

Bravo AF: 0.0740

Asia WGS AF: 0.201 AC: 696 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.28
PhyloP100		-0.10
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: rs5742692; hg19: chr12-102799598;