rs5009837

Variant names:

• chr12-102416491-T-C
• rs5009837
• NM_000618.5:c.402+3018A>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.402+3018A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.666 in 152,070 control chromosomes in the GnomAD database, including 33,991 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 0.67 (33991 hom., cov: 32)
• Consequence: IGF1 NM_000618.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00200
• Publications: 10 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).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF1	NM_000618.5	c.402+3018A>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.402+3018A>G		intron_variant	Intron 3 of 3	1	NM_000618.5	ENSP00000337612.7

Frequencies

GnomAD3 genomes AF: 0.666 AC: 101183 AN: 151952 Hom.: 33999 Cov.: 32

Gnomad AFR AF: 0.578

Gnomad AMI AF: 0.848

Gnomad AMR AF: 0.734

Gnomad ASJ AF: 0.719

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.654

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.709

Gnomad OTH AF: 0.677

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

GnomAD4 genome AF: 0.666 AC: 101204 AN: 152070 Hom.: 33991 Cov.: 32 AF XY: 0.666 AC XY: 49491 AN XY: 74328

African (AFR) AF: 0.577 AC: 23927 AN: 41458

American (AMR) AF: 0.734 AC: 11220 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.719 AC: 2495 AN: 3468

East Asian (EAS) AF: 0.558 AC: 2879 AN: 5164

South Asian (SAS) AF: 0.653 AC: 3138 AN: 4808

European-Finnish (FIN) AF: 0.657 AC: 6943 AN: 10574

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.709 AC: 48202 AN: 67992

Other (OTH) AF: 0.671 AC: 1418 AN: 2114

Alfa AF: 0.698 Hom.: 47776

Bravo AF: 0.666

Asia WGS AF: 0.573 AC: 1996 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.3
DANN	Benign	0.85
PhyloP100		0.0020
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs5009837; hg19: chr12-102810269;