12-102442288-C-T

Position:

• chr12-102442288-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000618.5(IGF1):​c.221-22598G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0273 in 152,044 control chromosomes in the GnomAD database, including 90 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 0.027 (90 hom., cov: 32)
• Consequence: IGF1 NM_000618.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.448

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=-0.78).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0273 (4147/152044) while in subpopulation AFR AF= 0.0411 (1703/41482). AF 95% confidence interval is 0.0394. There are 90 homozygotes in gnomad4. There are 1984 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 90 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGF1	NM_000618.5	c.221-22598G>A		intron_variant		ENST00000337514.11	NP_000609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGF1	ENST00000337514.11	c.221-22598G>A		intron_variant		1	NM_000618.5	ENSP00000337612.7

Frequencies

GnomAD3 genomes AF: 0.0273 AC: 4142 AN: 151922 Hom.: 89 Cov.: 32

Gnomad AFR AF: 0.0410

Gnomad AMI AF: 0.0604

Gnomad AMR AF: 0.0210

Gnomad ASJ AF: 0.0182

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00457

Gnomad FIN AF: 0.0331

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.0233

Gnomad OTH AF: 0.0216

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

GnomAD4 genome AF: 0.0273 AC: 4147 AN: 152044 Hom.: 90 Cov.: 32 AF XY: 0.0267 AC XY: 1984 AN XY: 74320

Gnomad4 AFR AF: 0.0411

Gnomad4 AMR AF: 0.0209

Gnomad4 ASJ AF: 0.0182

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00458

Gnomad4 FIN AF: 0.0331

Gnomad4 NFE AF: 0.0233

Gnomad4 OTH AF: 0.0213

Alfa AF: 0.0160 Hom.: 18

Bravo AF: 0.0269

Asia WGS AF: 0.00491 AC: 17 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.4
DANN	Benign	0.57

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: rs5742652; hg19: chr12-102836066;