rs11111272

Positions:

• chr12-102433663-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.221-13973C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.669 in 151,990 control chromosomes in the GnomAD database, including 34,218 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 0.67 (34218 hom., cov: 32)
• Consequence: IGF1 NM_000618.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0940

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGF1	NM_000618.5	c.221-13973C>G		intron_variant		ENST00000337514.11
LINC02456	XR_007063427.1	n.6800+10483G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGF1	ENST00000337514.11	c.221-13973C>G		intron_variant		1	NM_000618.5	P1
LINC02456	ENST00000704346.1	n.1176+10483G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.669 AC: 101594 AN: 151872 Hom.: 34227 Cov.: 32

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.808

Gnomad AMR AF: 0.735

Gnomad ASJ AF: 0.720

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.644

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.707

Gnomad OTH AF: 0.678

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

GnomAD4 genome AF: 0.669 AC: 101613 AN: 151990 Hom.: 34218 Cov.: 32 AF XY: 0.669 AC XY: 49673 AN XY: 74270

Gnomad4 AFR AF: 0.592

Gnomad4 AMR AF: 0.735

Gnomad4 ASJ AF: 0.720

Gnomad4 EAS AF: 0.557

Gnomad4 SAS AF: 0.643

Gnomad4 FIN AF: 0.657

Gnomad4 NFE AF: 0.707

Gnomad4 OTH AF: 0.672

Alfa AF: 0.675 Hom.: 4349

Bravo AF: 0.670

Asia WGS AF: 0.569 AC: 1981 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.12
DANN	Benign	0.61

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: rs11111272; hg19: chr12-102827441;