chr15-98704789-C-T

Variant names:

• chr15-98704789-C-T
• rs4966014
• NM_000875.5:c.95-2773C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000875.5(IGF1R):​c.95-2773C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.756 in 151,918 control chromosomes in the GnomAD database, including 44,056 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 0.76 (44056 hom., cov: 30)
• Consequence: IGF1R NM_000875.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• growth delay due to insulin-like growth factor I resistance

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF1R	NM_000875.5	c.95-2773C>T		intron_variant	Intron 1 of 20	ENST00000650285.1	NP_000866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGF1R	ENST00000650285.1	c.95-2773C>T		intron_variant	Intron 1 of 20		NM_000875.5	ENSP00000497069.1
IGF1R	ENST00000559925.5	n.95-2773C>T		intron_variant	Intron 1 of 9	1
IGF1R	ENST00000649865.1	c.95-2773C>T		intron_variant	Intron 1 of 20			ENSP00000496919.1

Frequencies

GnomAD3 genomes AF: 0.756 AC: 114690 AN: 151802 Hom.: 44013 Cov.: 30

Gnomad AFR AF: 0.887

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.749

Gnomad ASJ AF: 0.692

Gnomad EAS AF: 0.758

Gnomad SAS AF: 0.653

Gnomad FIN AF: 0.743

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.730

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

GnomAD4 genome AF: 0.756 AC: 114784 AN: 151918 Hom.: 44056 Cov.: 30 AF XY: 0.753 AC XY: 55938 AN XY: 74258

African (AFR) AF: 0.887 AC: 36751 AN: 41420

American (AMR) AF: 0.749 AC: 11418 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.692 AC: 2399 AN: 3466

East Asian (EAS) AF: 0.758 AC: 3895 AN: 5138

South Asian (SAS) AF: 0.653 AC: 3146 AN: 4820

European-Finnish (FIN) AF: 0.743 AC: 7840 AN: 10554

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.692 AC: 47013 AN: 67956

Other (OTH) AF: 0.725 AC: 1529 AN: 2110

Alfa AF: 0.715 Hom.: 97559

Bravo AF: 0.765

Asia WGS AF: 0.691 AC: 2406 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.073
DANN	Benign	0.71
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4966014; hg19: chr15-99248018;