Variant 15-98960571-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000875.5(IGF1R):c.*3129G>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 0.478 in 233,420 control chromosomes in the GnomAD database, including 27,453 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 16545 hom., cov: 33)

Exomes 𝑓: 0.52 ( 10908 hom. )

Consequence

IGF1R
NM_000875.5 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.529

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 15-98960571-G-T is Benign according to our data. Variant chr15-98960571-G-T is described in ClinVar as [Benign]. Clinvar id is 317546.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.592 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.*3129G>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.*3129G>T	3_prime_UTR_variant	21/21		NM_000875.5	ENSP00000497069	P4
SYNM-AS1	ENST00000559468.1 linkuse as main transcript	n.348+5418C>A	intron_variant, non_coding_transcript_variant		4
IGF1R	ENST00000649865.1 linkuse as main transcript	c.*3129G>T	3_prime_UTR_variant	21/21			ENSP00000496919	A1

Frequencies

GnomAD3 genomes

AF:

0.458

AC:

69631

AN:

151992

Hom.:

16535

Cov.:

show subpopulations

Gnomad AFR

AF:

0.324

Gnomad AMI

AF:

0.277

Gnomad AMR

AF:

0.455

Gnomad ASJ

AF:

0.521

Gnomad EAS

AF:

0.526

Gnomad SAS

AF:

0.610

Gnomad FIN

AF:

0.528

Gnomad MID

AF:

0.494

Gnomad NFE

AF:

0.512

Gnomad OTH

AF:

0.483

GnomAD4 exome

AF:

0.515

AC:

41907

AN:

81310

Hom.:

10908

Cov.:

AF XY:

0.518

AC XY:

19416

AN XY:

37478

show subpopulations

Gnomad4 AFR exome

AF:

0.329

Gnomad4 AMR exome

AF:

0.457

Gnomad4 ASJ exome

AF:

0.521

Gnomad4 EAS exome

AF:

0.579

Gnomad4 SAS exome

AF:

0.630

Gnomad4 FIN exome

AF:

0.544

Gnomad4 NFE exome

AF:

0.518

Gnomad4 OTH exome

AF:

0.503

GnomAD4 genome

AF:

0.458

AC:

69678

AN:

152110

Hom.:

16545

Cov.:

AF XY:

0.461

AC XY:

34277

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.324

Gnomad4 AMR

AF:

0.455

Gnomad4 ASJ

AF:

0.521

Gnomad4 EAS

AF:

0.526

Gnomad4 SAS

AF:

0.610

Gnomad4 FIN

AF:

0.528

Gnomad4 NFE

AF:

0.512

Gnomad4 OTH

AF:

0.486

Alfa

AF:

0.465

Hom.:

6490

Bravo

AF:

0.444

Asia WGS

AF:

0.540

AC:

1875

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 12, 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

-0.81

CADD

Benign

2.5

DANN

Benign

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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