chr12-102429772-C-G

Position:

• chr12-102429772-C-G

Variant summary

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

The ENST00000337514.11(IGF1):​c.221-10082G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0835 in 152,258 control chromosomes in the GnomAD database, including 740 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 0.083 (740 hom., cov: 32)
• Consequence: IGF1 ENST00000337514.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.537

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 (NFE) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGF1	NM_000618.5	c.221-10082G>C		intron_variant		ENST00000337514.11	NP_000609.1
LINC02456	XR_007063427.1	n.6800+6592C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGF1	ENST00000337514.11	c.221-10082G>C		intron_variant		1	NM_000618.5	ENSP00000337612	P1
LINC02456	ENST00000704346.1	n.1176+6592C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0835 AC: 12711 AN: 152140 Hom.: 740 Cov.: 32

Gnomad AFR AF: 0.0246

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.0954

Gnomad ASJ AF: 0.0983

Gnomad EAS AF: 0.00385

Gnomad SAS AF: 0.0292

Gnomad FIN AF: 0.0512

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.108

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

GnomAD4 genome AF: 0.0835 AC: 12706 AN: 152258 Hom.: 740 Cov.: 32 AF XY: 0.0803 AC XY: 5980 AN XY: 74450

Gnomad4 AFR AF: 0.0245

Gnomad4 AMR AF: 0.0953

Gnomad4 ASJ AF: 0.0983

Gnomad4 EAS AF: 0.00386

Gnomad4 SAS AF: 0.0288

Gnomad4 FIN AF: 0.0512

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.107

Alfa AF: 0.0949 Hom.: 84

Bravo AF: 0.0862

Asia WGS AF: 0.0140 AC: 49 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	0.41
DANN	Benign	0.43

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: rs5742665; hg19: chr12-102823550;