12-102412527-C-T

Variant names:

• chr12-102412527-C-T
• rs4764883
• NM_000618.5:c.402+6982G>A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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

Gnomad4 AFR AF: 0.445

Gnomad4 AMR AF: 0.720

Gnomad4 ASJ AF: 0.716

Gnomad4 EAS AF: 0.557

Gnomad4 SAS AF: 0.665

Gnomad4 FIN AF: 0.657

Gnomad4 NFE AF: 0.706

Gnomad4 OTH AF: 0.641

Alfa AF: 0.610 Hom.: 5166

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs4764883; hg19: chr12-102806305;