12-102469201-C-T

Variant names:

• chr12-102469201-C-T
• rs10778176
• NM_000618.5:c.220+6442G>A

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+6442G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 152,018 control chromosomes in the GnomAD database, including 7,911 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 0.32 (7911 hom., cov: 32)
• Consequence: IGF1 NM_000618.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.249
• Publications: 18 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF1	NM_000618.5	c.220+6442G>A		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+6442G>A		intron_variant	Intron 2 of 3	1	NM_000618.5	ENSP00000337612.7

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47834 AN: 151900 Hom.: 7885 Cov.: 32

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.291

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

GnomAD4 genome AF: 0.315 AC: 47922 AN: 152018 Hom.: 7911 Cov.: 32 AF XY: 0.316 AC XY: 23491 AN XY: 74332

African (AFR) AF: 0.402 AC: 16667 AN: 41420

American (AMR) AF: 0.238 AC: 3631 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 789 AN: 3470

East Asian (EAS) AF: 0.436 AC: 2252 AN: 5168

South Asian (SAS) AF: 0.288 AC: 1387 AN: 4822

European-Finnish (FIN) AF: 0.374 AC: 3953 AN: 10558

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.271 AC: 18395 AN: 67988

Other (OTH) AF: 0.296 AC: 626 AN: 2112

Alfa AF: 0.258 Hom.: 3061

Bravo AF: 0.312

Asia WGS AF: 0.410 AC: 1423 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.75
DANN	Benign	0.45
PhyloP100		-0.25
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: rs10778176; hg19: chr12-102862979;