12-102412527-C-T

Variant names:

• chr12-102412527-C-T
• rs4764883
• NM_000618.5:c.402+6982G>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.402+6982G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 152,012 control chromosomes in the GnomAD database, including 30,894 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 0.63 (30894 hom., cov: 32)
• Consequence: IGF1 NM_000618.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.34
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF1	NM_000618.5	c.402+6982G>A		intron_variant	Intron 3 of 3	ENST00000337514.11	NP_000609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGF1	ENST00000337514.11	c.402+6982G>A		intron_variant	Intron 3 of 3	1	NM_000618.5	ENSP00000337612.7

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95256 AN: 151894 Hom.: 30905 Cov.: 32

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.808

Gnomad AMR AF: 0.720

Gnomad ASJ AF: 0.716

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.706

Gnomad OTH AF: 0.647

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

GnomAD4 genome AF: 0.627 AC: 95266 AN: 152012 Hom.: 30894 Cov.: 32 AF XY: 0.629 AC XY: 46718 AN XY: 74288

African (AFR) AF: 0.445 AC: 18455 AN: 41432

American (AMR) AF: 0.720 AC: 10996 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.716 AC: 2485 AN: 3470

East Asian (EAS) AF: 0.557 AC: 2876 AN: 5168

South Asian (SAS) AF: 0.665 AC: 3208 AN: 4824

European-Finnish (FIN) AF: 0.657 AC: 6936 AN: 10550

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.706 AC: 48010 AN: 67980

Other (OTH) AF: 0.641 AC: 1355 AN: 2114

Alfa AF: 0.638 Hom.: 10197

Bravo AF: 0.624

Asia WGS AF: 0.570 AC: 1986 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.0080
DANN	Benign	0.43
PhyloP100		-3.3
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: rs4764883; hg19: chr12-102806305;