rs17727841

Positions:

• chr12-102415852-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.402+3657C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,126 control chromosomes in the GnomAD database, including 1,708 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 0.13 (1708 hom., cov: 31)
  • Exomes 𝑓: 0.080 (0 hom.)
• Consequence: IGF1 NM_000618.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.301

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGF1	NM_000618.5	c.402+3657C>G		intron_variant		ENST00000337514.11
LINC02456	XR_007063427.1	n.6690+1780G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGF1	ENST00000337514.11	c.402+3657C>G		intron_variant		1	NM_000618.5	P1
LINC02456	ENST00000704346.1	n.1067-7219G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20086 AN: 151896 Hom.: 1707 Cov.: 31

Gnomad AFR AF: 0.0331

Gnomad AMI AF: 0.0725

Gnomad AMR AF: 0.0920

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.153

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.135

GnomAD4 exome AF: 0.0804 AC: 9 AN: 112 Hom.: 0 AF XY: 0.0833 AC XY: 8 AN XY: 96

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0682

Gnomad4 OTH exome AF: 0.100

GnomAD4 genome AF: 0.132 AC: 20086 AN: 152014 Hom.: 1708 Cov.: 31 AF XY: 0.132 AC XY: 9836 AN XY: 74294

Gnomad4 AFR AF: 0.0331

Gnomad4 AMR AF: 0.0919

Gnomad4 ASJ AF: 0.156

Gnomad4 EAS AF: 0.167

Gnomad4 SAS AF: 0.169

Gnomad4 FIN AF: 0.205

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.135

Alfa AF: 0.161 Hom.: 307

Bravo AF: 0.118

Asia WGS AF: 0.147 AC: 509 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.68

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: rs17727841; hg19: chr12-102809630;