rs12313279

chr12-102452726-A-Gchr12-102452726-A-T

Variant summary

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

The NM_000618.5(IGF1):c.220+22917T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.679 in 152,050 control chromosomes in the GnomAD database, including 35,328 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 0.68 (35328 hom., cov: 32)
• Consequence: IGF1 NM_000618.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.129

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGF1	NM_000618.5	c.220+22917T>C		intron_variant		ENST00000337514.11
LINC02456	XR_007063427.1	n.6801-3061A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGF1	ENST00000337514.11	c.220+22917T>C		intron_variant		1	NM_000618.5	P1
LINC02456	ENST00000704346.1	n.1177-10002A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.680 AC: 103267 AN: 151932 Hom.: 35327 Cov.: 32

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.904

Gnomad AMR AF: 0.750

Gnomad ASJ AF: 0.730

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.652

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.705

Gnomad OTH AF: 0.689

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

GnomAD4 genome AF: 0.679 AC: 103299 AN: 152050 Hom.: 35328 Cov.: 32 AF XY: 0.679 AC XY: 50471 AN XY: 74322

Gnomad4 AFR AF: 0.630

Gnomad4 AMR AF: 0.750

Gnomad4 ASJ AF: 0.730

Gnomad4 EAS AF: 0.556

Gnomad4 SAS AF: 0.651

Gnomad4 FIN AF: 0.638

Gnomad4 NFE AF: 0.705

Gnomad4 OTH AF: 0.683

Alfa AF: 0.656 Hom.: 5050

Bravo AF: 0.685

Asia WGS AF: 0.573 AC: 1994 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	2.4
Dann	Benign	0.69

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: rs12313279; hg19: chr12-102846504;