Variant 15-98959298-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_000875.5(IGF1R):c.*1856C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.05 in 233,598 control chromosomes in the GnomAD database, including 374 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.052 ( 264 hom., cov: 33)

Exomes 𝑓: 0.045 ( 110 hom. )

Consequence

IGF1R
NM_000875.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.24

Variant links:

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]

IGF1R links:

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

SYNM-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 15-98959298-C-T is Benign according to our data. Variant chr15-98959298-C-T is described in ClinVar as [Benign]. Clinvar id is 317517.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0775 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGF1R	NM_000875.5 linkuse as main transcript	c.*1856C>T		3_prime_UTR_variant	21/21	ENST00000650285.1	NP_000866.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
IGF1R	ENST00000650285.1 linkuse as main transcript	c.*1856C>T	3_prime_UTR_variant	21/21		NM_000875.5	ENSP00000497069	P4
SYNM-AS1	ENST00000559468.1 linkuse as main transcript	n.349-4910G>A	intron_variant, non_coding_transcript_variant		4
IGF1R	ENST00000649865.1 linkuse as main transcript	c.*1856C>T	3_prime_UTR_variant	21/21			ENSP00000496919	A1

Frequencies

GnomAD3 genomes

AF:

0.0524

AC:

7975

AN:

152222

Hom.:

263

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0569

Gnomad AMI

AF:

0.198

Gnomad AMR

AF:

0.0811

Gnomad ASJ

AF:

0.0230

Gnomad EAS

AF:

0.0644

Gnomad SAS

AF:

0.0695

Gnomad FIN

AF:

0.0303

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0443

Gnomad OTH

AF:

0.0440

GnomAD4 exome

AF:

0.0454

AC:

3693

AN:

81258

Hom.:

110

Cov.:

AF XY:

0.0445

AC XY:

1665

AN XY:

37422

show subpopulations

Gnomad4 AFR exome

AF:

0.0648

Gnomad4 AMR exome

AF:

0.0880

Gnomad4 ASJ exome

AF:

0.0256

Gnomad4 EAS exome

AF:

0.0580

Gnomad4 SAS exome

AF:

0.0571

Gnomad4 FIN exome

AF:

0.0393

Gnomad4 NFE exome

AF:

0.0409

Gnomad4 OTH exome

AF:

0.0463

GnomAD4 genome

AF:

0.0524

AC:

7981

AN:

152340

Hom.:

264

Cov.:

AF XY:

0.0526

AC XY:

3918

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.0568

Gnomad4 AMR

AF:

0.0813

Gnomad4 ASJ

AF:

0.0230

Gnomad4 EAS

AF:

0.0640

Gnomad4 SAS

AF:

0.0696

Gnomad4 FIN

AF:

0.0303

Gnomad4 NFE

AF:

0.0443

Gnomad4 OTH

AF:

0.0440

Alfa

AF:

0.0517

Hom.:

133

Bravo

AF:

0.0558

Asia WGS

AF:

0.0810

AC:

281

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Growth delay due to insulin-like growth factor I resistance

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over