rs978458

Variant names:

• chr12-102408461-T-C
• rs978458
• NM_000618.5:c.403-5895A>G

Variant summary

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

The NM_000618.5(IGF1):​c.403-5895A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.694 in 152,056 control chromosomes in the GnomAD database, including 36,951 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 0.69 (36951 hom., cov: 32)
• Consequence: IGF1 NM_000618.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.404
• Publications: 37 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 = 0.743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF1	NM_000618.5	c.403-5895A>G		intron_variant	Intron 3 of 3	ENST00000337514.11	NP_000609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGF1	ENST00000337514.11	c.403-5895A>G		intron_variant	Intron 3 of 3	1	NM_000618.5	ENSP00000337612.7

Frequencies

GnomAD3 genomes AF: 0.695 AC: 105525 AN: 151938 Hom.: 36949 Cov.: 32

Gnomad AFR AF: 0.622

Gnomad AMI AF: 0.909

Gnomad AMR AF: 0.755

Gnomad ASJ AF: 0.734

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.685

Gnomad FIN AF: 0.689

Gnomad MID AF: 0.726

Gnomad NFE AF: 0.732

Gnomad OTH AF: 0.699

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

GnomAD4 genome AF: 0.694 AC: 105557 AN: 152056 Hom.: 36951 Cov.: 32 AF XY: 0.694 AC XY: 51600 AN XY: 74316

African (AFR) AF: 0.622 AC: 25794 AN: 41472

American (AMR) AF: 0.754 AC: 11529 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.734 AC: 2546 AN: 3470

East Asian (EAS) AF: 0.557 AC: 2868 AN: 5148

South Asian (SAS) AF: 0.684 AC: 3295 AN: 4816

European-Finnish (FIN) AF: 0.689 AC: 7284 AN: 10574

Middle Eastern (MID) AF: 0.723 AC: 211 AN: 292

European-Non Finnish (NFE) AF: 0.732 AC: 49737 AN: 67970

Other (OTH) AF: 0.693 AC: 1464 AN: 2114

Alfa AF: 0.719 Hom.: 125070

Bravo AF: 0.694

Asia WGS AF: 0.588 AC: 2047 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	0.62
DANN	Benign	0.38
PhyloP100		-0.40
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: rs978458; hg19: chr12-102802239;