chr12-102402744-G-C

Position:

• chr12-102402744-G-C

Variant summary

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

The NM_000618.5(IGF1):​c.403-178C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.771 in 623,316 control chromosomes in the GnomAD database, including 187,764 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 0.75 (43833 hom., cov: 31)
  • Exomes 𝑓: 0.78 (143931 hom.)
• Consequence: IGF1 NM_000618.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.419

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGF1	NM_000618.5	c.403-178C>G		intron_variant		ENST00000337514.11
LINC02456	XR_007063427.1	n.697-1369G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGF1	ENST00000337514.11	c.403-178C>G		intron_variant		1	NM_000618.5	P1
LINC02456	ENST00000704346.1	n.1067-20327G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.754 AC: 114609 AN: 151940 Hom.: 43833 Cov.: 31

Gnomad AFR AF: 0.640

Gnomad AMI AF: 0.947

Gnomad AMR AF: 0.794

Gnomad ASJ AF: 0.752

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.694

Gnomad FIN AF: 0.832

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.819

Gnomad OTH AF: 0.759

GnomAD4 exome AF: 0.776 AC: 365773 AN: 471258 Hom.: 143931 AF XY: 0.773 AC XY: 194808 AN XY: 251966

Gnomad4 AFR exome AF: 0.644

Gnomad4 AMR exome AF: 0.772

Gnomad4 ASJ exome AF: 0.745

Gnomad4 EAS exome AF: 0.537

Gnomad4 SAS exome AF: 0.713

Gnomad4 FIN exome AF: 0.820

Gnomad4 NFE exome AF: 0.819

Gnomad4 OTH exome AF: 0.765

GnomAD4 genome AF: 0.754 AC: 114637 AN: 152058 Hom.: 43833 Cov.: 31 AF XY: 0.754 AC XY: 56079 AN XY: 74344

Gnomad4 AFR AF: 0.640

Gnomad4 AMR AF: 0.793

Gnomad4 ASJ AF: 0.752

Gnomad4 EAS AF: 0.557

Gnomad4 SAS AF: 0.692

Gnomad4 FIN AF: 0.832

Gnomad4 NFE AF: 0.819

Gnomad4 OTH AF: 0.752

Alfa AF: 0.738 Hom.: 2644

Bravo AF: 0.743

Asia WGS AF: 0.590 AC: 2053 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.2
DANN	Benign	0.40

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: rs1520220; hg19: chr12-102796522;