chr12-102453298-A-G

Position:

• chr12-102453298-A-G

Variant summary

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

The ENST00000337514.11(IGF1):​c.220+22345T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.943 in 152,270 control chromosomes in the GnomAD database, including 67,751 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 0.94 (67751 hom., cov: 32)
• Consequence: IGF1 ENST00000337514.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0370

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGF1	NM_000618.5	c.220+22345T>C		intron_variant		ENST00000337514.11	NP_000609.1
LINC02456	XR_007063427.1	n.6801-2489A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGF1	ENST00000337514.11	c.220+22345T>C		intron_variant		1	NM_000618.5	ENSP00000337612	P1
LINC02456	ENST00000704346.1	n.1177-9430A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.943 AC: 143483 AN: 152152 Hom.: 67697 Cov.: 32

Gnomad AFR AF: 0.954

Gnomad AMI AF: 0.981

Gnomad AMR AF: 0.944

Gnomad ASJ AF: 0.898

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.908

Gnomad FIN AF: 0.975

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.932

Gnomad OTH AF: 0.932

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

GnomAD4 genome AF: 0.943 AC: 143596 AN: 152270 Hom.: 67751 Cov.: 32 AF XY: 0.945 AC XY: 70332 AN XY: 74442

Gnomad4 AFR AF: 0.954

Gnomad4 AMR AF: 0.944

Gnomad4 ASJ AF: 0.898

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.907

Gnomad4 FIN AF: 0.975

Gnomad4 NFE AF: 0.932

Gnomad4 OTH AF: 0.933

Alfa AF: 0.931 Hom.: 86434

Bravo AF: 0.942

Asia WGS AF: 0.960 AC: 3336 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.44

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: rs2033178; hg19: chr12-102847076;