rs11111262

Variant names:

• chr12-102404399-G-A
• rs11111262
• NM_000618.5:c.403-1833C>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.403-1833C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.071 in 152,184 control chromosomes in the GnomAD database, including 506 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 0.071 (506 hom., cov: 32)
• Consequence: IGF1 NM_000618.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14
• Publications: 9 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 (EAS) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF1	NM_000618.5	c.403-1833C>T		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.403-1833C>T		intron_variant	Intron 3 of 3	1	NM_000618.5	ENSP00000337612.7

Frequencies

GnomAD3 genomes AF: 0.0710 AC: 10804 AN: 152066 Hom.: 505 Cov.: 32

Gnomad AFR AF: 0.0184

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0541

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.0603

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0957

Gnomad OTH AF: 0.0748

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

GnomAD4 genome AF: 0.0710 AC: 10805 AN: 152184 Hom.: 506 Cov.: 32 AF XY: 0.0700 AC XY: 5207 AN XY: 74400

African (AFR) AF: 0.0183 AC: 761 AN: 41524

American (AMR) AF: 0.0541 AC: 827 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 478 AN: 3468

East Asian (EAS) AF: 0.167 AC: 864 AN: 5164

South Asian (SAS) AF: 0.105 AC: 507 AN: 4820

European-Finnish (FIN) AF: 0.0603 AC: 639 AN: 10598

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0957 AC: 6507 AN: 67998

Other (OTH) AF: 0.0754 AC: 159 AN: 2108

Alfa AF: 0.0731 Hom.: 98

Bravo AF: 0.0692

Asia WGS AF: 0.120 AC: 418 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	12
DANN	Benign	0.61
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: rs11111262; hg19: chr12-102798177;