Variant rs951715 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000875.5(IGF1R):c.1828+42G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 1,486,490 control chromosomes in the GnomAD database, including 304,719 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 0.64 ( 31317 hom., cov: 34)

Exomes 𝑓: 0.64 ( 273402 hom. )

Consequence

IGF1R
NM_000875.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.92

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.71 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.1828+42G>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.1828+42G>A	intron_variant		NM_000875.5	ENSP00000497069	P4
IGF1R	ENST00000559925.5 linkuse as main transcript	n.1828+42G>A	intron_variant, non_coding_transcript_variant	1
IGF1R	ENST00000649865.1 linkuse as main transcript	c.1828+42G>A	intron_variant			ENSP00000496919	A1
IGF1R	ENST00000560144.1 linkuse as main transcript	c.107+42G>A	intron_variant, NMD_transcript_variant	3		ENSP00000456950

Frequencies

GnomAD3 genomes

AF:

0.640

AC:

97321

AN:

152064

Hom.:

31276

Cov.:

show subpopulations

Gnomad AFR

AF:

0.654

Gnomad AMI

AF:

0.693

Gnomad AMR

AF:

0.604

Gnomad ASJ

AF:

0.647

Gnomad EAS

AF:

0.508

Gnomad SAS

AF:

0.729

Gnomad FIN

AF:

0.652

Gnomad MID

AF:

0.715

Gnomad NFE

AF:

0.639

Gnomad OTH

AF:

0.661

GnomAD3 exomes

AF:

0.636

AC:

159641

AN:

250942

Hom.:

51272

AF XY:

0.643

AC XY:

87301

AN XY:

135692

show subpopulations

Gnomad AFR exome

AF:

0.650

Gnomad AMR exome

AF:

0.587

Gnomad ASJ exome

AF:

0.656

Gnomad EAS exome

AF:

0.494

Gnomad SAS exome

AF:

0.739

Gnomad FIN exome

AF:

0.658

Gnomad NFE exome

AF:

0.638

Gnomad OTH exome

AF:

0.652

GnomAD4 exome

AF:

0.640

AC:

853579

AN:

1334306

Hom.:

273402

Cov.:

AF XY:

0.643

AC XY:

431534

AN XY:

670868

show subpopulations

Gnomad4 AFR exome

AF:

0.656

Gnomad4 AMR exome

AF:

0.589

Gnomad4 ASJ exome

AF:

0.656

Gnomad4 EAS exome

AF:

0.550

Gnomad4 SAS exome

AF:

0.737

Gnomad4 FIN exome

AF:

0.654

Gnomad4 NFE exome

AF:

0.635

Gnomad4 OTH exome

AF:

0.651

GnomAD4 genome

AF:

0.640

AC:

97419

AN:

152184

Hom.:

31317

Cov.:

AF XY:

0.640

AC XY:

47611

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.654

Gnomad4 AMR

AF:

0.604

Gnomad4 ASJ

AF:

0.647

Gnomad4 EAS

AF:

0.508

Gnomad4 SAS

AF:

0.730

Gnomad4 FIN

AF:

0.652

Gnomad4 NFE

AF:

0.639

Gnomad4 OTH

AF:

0.665

Alfa

AF:

0.621

Hom.:

8195

Bravo

AF:

0.637

Asia WGS

AF:

0.674

AC:

2342

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.0030

DANN

Benign

0.49

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