12-102442288-C-T

Variant names:

• chr12-102442288-C-T
• rs5742652
• NM_000618.5:c.221-22598G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 90 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF1	NM_000618.5	c.221-22598G>A		intron_variant	Intron 2 of 3	ENST00000337514.11	NP_000609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGF1	ENST00000337514.11	c.221-22598G>A		intron_variant	Intron 2 of 3	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

African (AFR) AF: 0.0411 AC: 1703 AN: 41482

American (AMR) AF: 0.0209 AC: 320 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0182 AC: 63 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00458 AC: 22 AN: 4806

European-Finnish (FIN) AF: 0.0331 AC: 350 AN: 10570

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0233 AC: 1586 AN: 67958

Other (OTH) AF: 0.0213 AC: 45 AN: 2108

Alfa AF: 0.0166 Hom.: 19

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
PhyloP100		-0.45
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs5742652; hg19: chr12-102836066;