12-102407157-C-T

Variant names:

• chr12-102407157-C-T
• rs6539035
• NM_000618.5:c.403-4591G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000618.5(IGF1):​c.403-4591G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.783 in 142,272 control chromosomes in the GnomAD database, including 42,727 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 0.78 (42727 hom., cov: 24)
• Consequence: IGF1 NM_000618.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.469

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF1	NM_000618.5	c.403-4591G>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.403-4591G>A		intron_variant	Intron 3 of 3	1	NM_000618.5	ENSP00000337612.7

Frequencies

GnomAD3 genomes AF: 0.783 AC: 111379 AN: 142196 Hom.: 42702 Cov.: 24

Gnomad AFR AF: 0.779

Gnomad AMI AF: 0.913

Gnomad AMR AF: 0.849

Gnomad ASJ AF: 0.762

Gnomad EAS AF: 0.846

Gnomad SAS AF: 0.769

Gnomad FIN AF: 0.799

Gnomad MID AF: 0.748

Gnomad NFE AF: 0.765

Gnomad OTH AF: 0.788

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

GnomAD4 genome AF: 0.783 AC: 111440 AN: 142272 Hom.: 42727 Cov.: 24 AF XY: 0.787 AC XY: 54184 AN XY: 68866

Gnomad4 AFR AF: 0.779

Gnomad4 AMR AF: 0.849

Gnomad4 ASJ AF: 0.762

Gnomad4 EAS AF: 0.846

Gnomad4 SAS AF: 0.768

Gnomad4 FIN AF: 0.799

Gnomad4 NFE AF: 0.765

Gnomad4 OTH AF: 0.788

Alfa AF: 0.757 Hom.: 7192

Bravo AF: 0.771

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.78
DANN	Benign	0.22

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: rs6539035; hg19: chr12-102800935;