rs9989002

Positions:

• chr12-102456445-A-G
• chr12-102456445-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_000618.5(IGF1):​c.220+19198T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.749 in 152,064 control chromosomes in the GnomAD database, including 42,806 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 (42806 hom., cov: 31)
• Consequence: IGF1 NM_000618.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0250

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.82 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGF1	NM_000618.5	c.220+19198T>C		intron_variant		ENST00000337514.11
LINC02456	XR_007063427.1	n.7459A>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+19198T>C		intron_variant		1	NM_000618.5	P1
LINC02456	ENST00000704346.1	n.1177-6283A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.749 AC: 113829 AN: 151946 Hom.: 42769 Cov.: 31

Gnomad AFR AF: 0.762

Gnomad AMI AF: 0.904

Gnomad AMR AF: 0.832

Gnomad ASJ AF: 0.742

Gnomad EAS AF: 0.839

Gnomad SAS AF: 0.732

Gnomad FIN AF: 0.716

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.720

Gnomad OTH AF: 0.768

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

GnomAD4 genome AF: 0.749 AC: 113918 AN: 152064 Hom.: 42806 Cov.: 31 AF XY: 0.752 AC XY: 55901 AN XY: 74346

Gnomad4 AFR AF: 0.762

Gnomad4 AMR AF: 0.833

Gnomad4 ASJ AF: 0.742

Gnomad4 EAS AF: 0.839

Gnomad4 SAS AF: 0.731

Gnomad4 FIN AF: 0.716

Gnomad4 NFE AF: 0.720

Gnomad4 OTH AF: 0.768

Alfa AF: 0.725 Hom.: 5781

Bravo AF: 0.762

Asia WGS AF: 0.786 AC: 2731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	15
DANN	Benign	0.77
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs9989002; hg19: chr12-102850223;