12-102469201-C-T

Position:

• chr12-102469201-C-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+6442G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 152,018 control chromosomes in the GnomAD database, including 7,911 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 0.32 (7911 hom., cov: 32)
• Consequence: IGF1 NM_000618.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.249

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:):

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 (EAS) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGF1	NM_000618.5	c.220+6442G>A		intron_variant		ENST00000337514.11
LINC02456	XR_007063427.1	n.20215C>T		non_coding_transcript_exon_variant	11/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGF1	ENST00000337514.11	c.220+6442G>A		intron_variant		1	NM_000618.5	P1

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47834 AN: 151900 Hom.: 7885 Cov.: 32

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.291

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

GnomAD4 genome AF: 0.315 AC: 47922 AN: 152018 Hom.: 7911 Cov.: 32 AF XY: 0.316 AC XY: 23491 AN XY: 74332

Gnomad4 AFR AF: 0.402

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.436

Gnomad4 SAS AF: 0.288

Gnomad4 FIN AF: 0.374

Gnomad4 NFE AF: 0.271

Gnomad4 OTH AF: 0.296

Alfa AF: 0.255 Hom.: 2760

Bravo AF: 0.312

Asia WGS AF: 0.410 AC: 1423 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	0.75
DANN	Benign	0.45

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: rs10778176; hg19: chr12-102862979;