rs8038056

chr15-98939699-A-Gchr15-98939699-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000875.5(IGF1R):c.3457+339A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,188 control chromosomes in the GnomAD database, including 1,558 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 0.13 (1558 hom., cov: 33)
• Consequence: IGF1R NM_000875.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.541

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGF1R	NM_000875.5	c.3457+339A>G		intron_variant		ENST00000650285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGF1R	ENST00000650285.1	c.3457+339A>G		intron_variant			NM_000875.5	P4
IGF1R	ENST00000649865.1	c.3454+339A>G		intron_variant				A1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19242 AN: 152070 Hom.: 1541 Cov.: 33

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.0469

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0875

Gnomad OTH AF: 0.152

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.127 AC: 19285 AN: 152188 Hom.: 1558 Cov.: 33 AF XY: 0.133 AC XY: 9919 AN XY: 74422

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.252

Gnomad4 ASJ AF: 0.0469

Gnomad4 EAS AF: 0.344

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.0875

Gnomad4 OTH AF: 0.161

Alfa AF: 0.0998 Hom.: 2014

Bravo AF: 0.137

Asia WGS AF: 0.286 AC: 995 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	6.7
Dann	Benign	0.78

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: rs8038056; hg19: chr15-99482928;