rs2195240

Positions:

• chr12-102462869-A-G
• chr12-102462869-A-T

Variant summary

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

The ENST00000337514.11(IGF1):​c.220+12774T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 152,102 control chromosomes in the GnomAD database, including 5,485 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 0.26 (5485 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IGF1 ENST00000337514.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.304

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=-0.52).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGF1	NM_000618.5	c.220+12774T>C		intron_variant		ENST00000337514.11	NP_000609.1
LINC02456	XR_007063427.1	n.13883A>G		non_coding_transcript_exon_variant	11/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGF1	ENST00000337514.11	c.220+12774T>C		intron_variant		1	NM_000618.5	ENSP00000337612	P1
LINC02456	ENST00000704346.1	n.1318A>G		non_coding_transcript_exon_variant	11/11

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39948 AN: 151984 Hom.: 5461 Cov.: 32

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.244

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.263 AC: 40016 AN: 152102 Hom.: 5485 Cov.: 32 AF XY: 0.265 AC XY: 19706 AN XY: 74346

Gnomad4 AFR AF: 0.293

Gnomad4 AMR AF: 0.205

Gnomad4 ASJ AF: 0.204

Gnomad4 EAS AF: 0.434

Gnomad4 SAS AF: 0.283

Gnomad4 FIN AF: 0.334

Gnomad4 NFE AF: 0.239

Gnomad4 OTH AF: 0.250

Alfa AF: 0.245 Hom.: 918

Bravo AF: 0.256

Asia WGS AF: 0.402 AC: 1397 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	12
DANN	Benign	0.71

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: rs2195240; hg19: chr12-102856647; COSMIC: COSV61034292;