12-102471274-A-T

Variant names:

• chr12-102471274-A-T
• rs10860869
• NM_000618.5:c.220+4369T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000618.5(IGF1):​c.220+4369T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 152,050 control chromosomes in the GnomAD database, including 6,717 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 0.29 (6717 hom., cov: 32)
• Consequence: IGF1 NM_000618.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06
• Publications: 14 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=-0.52).
• 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 rank	MANE	Protein	UniProt
IGF1	NM_000618.5	c.220+4369T>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.220+4369T>A		intron_variant	Intron 2 of 3	1	NM_000618.5	ENSP00000337612.7

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44522 AN: 151932 Hom.: 6694 Cov.: 32

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.293 AC: 44602 AN: 152050 Hom.: 6717 Cov.: 32 AF XY: 0.295 AC XY: 21953 AN XY: 74308

African (AFR) AF: 0.322 AC: 13348 AN: 41488

American (AMR) AF: 0.232 AC: 3549 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 794 AN: 3468

East Asian (EAS) AF: 0.436 AC: 2250 AN: 5156

South Asian (SAS) AF: 0.290 AC: 1398 AN: 4816

European-Finnish (FIN) AF: 0.374 AC: 3953 AN: 10564

Middle Eastern (MID) AF: 0.223 AC: 65 AN: 292

European-Non Finnish (NFE) AF: 0.272 AC: 18495 AN: 67966

Other (OTH) AF: 0.280 AC: 590 AN: 2110

Alfa AF: 0.171 Hom.: 351

Bravo AF: 0.285

Asia WGS AF: 0.411 AC: 1425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	12
DANN	Benign	0.84
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs10860869; hg19: chr12-102865052;