rs5742632

Positions:

• chr12-102462696-A-G

Variant summary

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

The NM_000618.5(IGF1):​c.220+12947T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 152,074 control chromosomes in the GnomAD database, including 5,448 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 (5448 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: IGF1 NM_000618.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0880

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGF1	NM_000618.5	c.220+12947T>C		intron_variant		ENST00000337514.11
LINC02456	XR_007063427.1	n.13710A>G		non_coding_transcript_exon_variant	11/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGF1	ENST00000337514.11	c.220+12947T>C		intron_variant		1	NM_000618.5	P1
LINC02456	ENST00000704346.1	n.1177-32A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39803 AN: 151956 Hom.: 5424 Cov.: 32

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.0791

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.284

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 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.262 AC: 39871 AN: 152074 Hom.: 5448 Cov.: 32 AF XY: 0.264 AC XY: 19639 AN XY: 74318

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.203

Gnomad4 EAS AF: 0.433

Gnomad4 SAS AF: 0.284

Gnomad4 FIN AF: 0.334

Gnomad4 NFE AF: 0.239

Gnomad4 OTH AF: 0.250

Alfa AF: 0.242 Hom.: 9521

Bravo AF: 0.255

Asia WGS AF: 0.402 AC: 1395 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	8.1
DANN	Benign	0.64

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: rs5742632; hg19: chr12-102856474;