rs12821878

Variant names:

• chr12-102473889-G-A
• rs12821878
• NM_000618.5:c.220+1754C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-102473889-G-A
• chr12-102473889-G-T

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+1754C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,048 control chromosomes in the GnomAD database, including 2,834 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 0.17 (2834 hom., cov: 32)
• Consequence: IGF1 NM_000618.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.184
• Publications: 27 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF1	NM_000618.5	c.220+1754C>T		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+1754C>T		intron_variant	Intron 2 of 3	1	NM_000618.5	ENSP00000337612.7

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26149 AN: 151932 Hom.: 2837 Cov.: 32

Gnomad AFR AF: 0.0441

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.0616

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.172

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

GnomAD4 genome AF: 0.172 AC: 26144 AN: 152048 Hom.: 2834 Cov.: 32 AF XY: 0.173 AC XY: 12832 AN XY: 74308

African (AFR) AF: 0.0439 AC: 1824 AN: 41502

American (AMR) AF: 0.271 AC: 4145 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 727 AN: 3468

East Asian (EAS) AF: 0.0616 AC: 319 AN: 5182

South Asian (SAS) AF: 0.248 AC: 1190 AN: 4794

European-Finnish (FIN) AF: 0.175 AC: 1847 AN: 10570

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15428 AN: 67942

Other (OTH) AF: 0.170 AC: 359 AN: 2114

Alfa AF: 0.213 Hom.: 4903

Bravo AF: 0.171

Asia WGS AF: 0.137 AC: 477 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.63
DANN	Benign	0.63
PhyloP100		-0.18
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: rs12821878; hg19: chr12-102867667;