12-102477481-C-T

Position:

• chr12-102477481-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.64-1682G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 151,154 control chromosomes in the GnomAD database, including 43,105 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 0.74 (43105 hom., cov: 27)
• Consequence: IGF1 NM_000618.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGF1	NM_000618.5	c.64-1682G>A		intron_variant		ENST00000337514.11	NP_000609.1
LINC02456	XR_007063427.1	n.28495C>T		non_coding_transcript_exon_variant	11/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGF1	ENST00000337514.11	c.64-1682G>A		intron_variant		1	NM_000618.5	ENSP00000337612	P1

Frequencies

GnomAD3 genomes AF: 0.745 AC: 112498 AN: 151044 Hom.: 43104 Cov.: 27

Gnomad AFR AF: 0.551

Gnomad AMI AF: 0.801

Gnomad AMR AF: 0.787

Gnomad ASJ AF: 0.786

Gnomad EAS AF: 0.637

Gnomad SAS AF: 0.747

Gnomad FIN AF: 0.813

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.846

Gnomad OTH AF: 0.772

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

GnomAD4 genome AF: 0.745 AC: 112542 AN: 151154 Hom.: 43105 Cov.: 27 AF XY: 0.744 AC XY: 54840 AN XY: 73722

Gnomad4 AFR AF: 0.551

Gnomad4 AMR AF: 0.787

Gnomad4 ASJ AF: 0.786

Gnomad4 EAS AF: 0.637

Gnomad4 SAS AF: 0.747

Gnomad4 FIN AF: 0.813

Gnomad4 NFE AF: 0.846

Gnomad4 OTH AF: 0.768

Alfa AF: 0.826 Hom.: 66576

Bravo AF: 0.730

Asia WGS AF: 0.681 AC: 2368 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.20
DANN	Benign	0.38

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: rs2162679; hg19: chr12-102871259;