Variant rs2593053 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_000875.5(IGF1R):c.3723-34G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 1,612,068 control chromosomes in the GnomAD database, including 122,698 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.32 ( 8442 hom., cov: 33)

Exomes 𝑓: 0.39 ( 114256 hom. )

Consequence

IGF1R
NM_000875.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.38

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 15-98957027-G-A is Benign according to our data. Variant chr15-98957027-G-A is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.399 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.3723-34G>A		intron_variant		ENST00000650285.1	NP_000866.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
IGF1R	ENST00000650285.1 linkuse as main transcript	c.3723-34G>A	intron_variant		NM_000875.5	ENSP00000497069	P4
SYNM-AS1	ENST00000559468.1 linkuse as main transcript	n.349-2639C>T	intron_variant, non_coding_transcript_variant	4
IGF1R	ENST00000649865.1 linkuse as main transcript	c.3720-34G>A	intron_variant			ENSP00000496919	A1
IGF1R	ENST00000558751.1 linkuse as main transcript	n.317-34G>A	intron_variant, non_coding_transcript_variant	4

Frequencies

GnomAD3 genomes

AF:

0.316

AC:

48009

AN:

151968

Hom.:

8444

Cov.:

show subpopulations

Gnomad AFR

AF:

0.161

Gnomad AMI

AF:

0.250

Gnomad AMR

AF:

0.297

Gnomad ASJ

AF:

0.451

Gnomad EAS

AF:

0.282

Gnomad SAS

AF:

0.392

Gnomad FIN

AF:

0.325

Gnomad MID

AF:

0.389

Gnomad NFE

AF:

0.403

Gnomad OTH

AF:

0.344

GnomAD3 exomes

AF:

0.353

AC:

88485

AN:

250576

Hom.:

16521

AF XY:

0.364

AC XY:

49259

AN XY:

135476

show subpopulations

Gnomad AFR exome

AF:

0.154

Gnomad AMR exome

AF:

0.253

Gnomad ASJ exome

AF:

0.454

Gnomad EAS exome

AF:

0.271

Gnomad SAS exome

AF:

0.398

Gnomad FIN exome

AF:

0.342

Gnomad NFE exome

AF:

0.406

Gnomad OTH exome

AF:

0.372

GnomAD4 exome

AF:

0.391

AC:

571370

AN:

1459982

Hom.:

114256

Cov.:

AF XY:

0.393

AC XY:

285246

AN XY:

726350

show subpopulations

Gnomad4 AFR exome

AF:

0.150

Gnomad4 AMR exome

AF:

0.260

Gnomad4 ASJ exome

AF:

0.459

Gnomad4 EAS exome

AF:

0.319

Gnomad4 SAS exome

AF:

0.395

Gnomad4 FIN exome

AF:

0.345

Gnomad4 NFE exome

AF:

0.407

Gnomad4 OTH exome

AF:

0.385

GnomAD4 genome

AF:

0.316

AC:

48010

AN:

152086

Hom.:

8442

Cov.:

AF XY:

0.311

AC XY:

23159

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.160

Gnomad4 AMR

AF:

0.296

Gnomad4 ASJ

AF:

0.451

Gnomad4 EAS

AF:

0.283

Gnomad4 SAS

AF:

0.393

Gnomad4 FIN

AF:

0.325

Gnomad4 NFE

AF:

0.403

Gnomad4 OTH

AF:

0.341

Alfa

AF:

0.388

Hom.:

12514

Bravo

AF:

0.307

Asia WGS

AF:

0.294

AC:

1022

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.86

DANN

Benign

0.76

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over