rs3743251

Variant names:

• chr15-98960900-G-A
• rs3743251
• NM_000875.5:c.*3458G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-98960900-G-A
• chr15-98960900-G-C
• chr15-98960900-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000875.5(IGF1R):​c.*3458G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 233,166 control chromosomes in the GnomAD database, including 3,353 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1903 hom., cov: 33)
  • Exomes 𝑓: 0.18 (1450 hom.)
• Consequence: IGF1R NM_000875.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.118

Genes affected

IGF1R (HGNC:5465): (insulin like growth factor 1 receptor) This receptor binds insulin-like growth factor with a high affinity. It has tyrosine kinase activity. The insulin-like growth factor I receptor plays a critical role in transformation events. Cleavage of the precursor generates alpha and beta subunits. It is highly overexpressed in most malignant tissues where it functions as an anti-apoptotic agent by enhancing cell survival. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, May 2014]

SYNM-AS1 (HGNC:55421): (SYNM antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 15-98960900-G-A is Benign according to our data. Variant chr15-98960900-G-A is described in ClinVar as [Benign]. Clinvar id is 317557.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF1R	NM_000875.5	c.*3458G>A		3_prime_UTR_variant	Exon 21 of 21	ENST00000650285.1	NP_000866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGF1R	ENST00000650285.1	c.*3458G>A		3_prime_UTR_variant	Exon 21 of 21		NM_000875.5	ENSP00000497069.1
IGF1R	ENST00000649865.1	c.*3458G>A		3_prime_UTR_variant	Exon 21 of 21			ENSP00000496919.1
SYNM-AS1	ENST00000559468.1	n.348+5089C>T		intron_variant	Intron 3 of 3	4

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22753 AN: 151386 Hom.: 1906 Cov.: 33

Gnomad AFR AF: 0.0994

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.158

GnomAD4 exome AF: 0.176 AC: 14382 AN: 81670 Hom.: 1450 Cov.: 0 AF XY: 0.175 AC XY: 6590 AN XY: 37672

Gnomad4 AFR exome AF: 0.0949

Gnomad4 AMR exome AF: 0.197

Gnomad4 ASJ exome AF: 0.192

Gnomad4 EAS exome AF: 0.336

Gnomad4 SAS exome AF: 0.195

Gnomad4 FIN exome AF: 0.101

Gnomad4 NFE exome AF: 0.146

Gnomad4 OTH exome AF: 0.160

GnomAD4 genome AF: 0.150 AC: 22746 AN: 151496 Hom.: 1903 Cov.: 33 AF XY: 0.155 AC XY: 11481 AN XY: 74038

Gnomad4 AFR AF: 0.0992

Gnomad4 AMR AF: 0.203

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.380

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.145

Gnomad4 OTH AF: 0.156

Alfa AF: 0.150 Hom.: 1642

Bravo AF: 0.151

Asia WGS AF: 0.244 AC: 848 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Growth delay due to insulin-like growth factor I resistance Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.2
DANN	Benign	0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs3743251; hg19: chr15-99504129; COSMIC: COSV51269833; COSMIC: COSV51269833;