chr15-98653016-C-T

Variant names:

• chr15-98653016-C-T
• rs874305
• NM_000875.5:c.94+3341C>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.94+3341C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 150,580 control chromosomes in the GnomAD database, including 12,812 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 0.41 (12812 hom., cov: 30)
• Consequence: IGF1R NM_000875.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0830
• Publications: 3 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

ENSG00000278022 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000875.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF1R	NM_000875.5	MANE Select	c.94+3341C>T		intron	N/A	NP_000866.1
	IGF1R	NM_001291858.2		c.94+3341C>T		intron	N/A	NP_001278787.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF1R	ENST00000650285.1	MANE Select	c.94+3341C>T		intron	N/A	ENSP00000497069.1
	IGF1R	ENST00000559925.5	TSL:1	n.94+3341C>T		intron	N/A
	IGF1R	ENST00000649865.1		c.94+3341C>T		intron	N/A	ENSP00000496919.1

Frequencies

GnomAD3 genomes AF: 0.411 AC: 61793 AN: 150466 Hom.: 12799 Cov.: 30

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.378

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.368

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

GnomAD4 genome AF: 0.411 AC: 61845 AN: 150580 Hom.: 12812 Cov.: 30 AF XY: 0.414 AC XY: 30387 AN XY: 73408

African (AFR) AF: 0.441 AC: 18022 AN: 40902

American (AMR) AF: 0.360 AC: 5448 AN: 15130

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1040 AN: 3454

East Asian (EAS) AF: 0.377 AC: 1932 AN: 5122

South Asian (SAS) AF: 0.347 AC: 1653 AN: 4764

European-Finnish (FIN) AF: 0.504 AC: 5108 AN: 10128

Middle Eastern (MID) AF: 0.371 AC: 106 AN: 286

European-Non Finnish (NFE) AF: 0.403 AC: 27319 AN: 67786

Other (OTH) AF: 0.373 AC: 781 AN: 2096

Alfa AF: 0.411 Hom.: 1548

Bravo AF: 0.399

Asia WGS AF: 0.383 AC: 1334 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.68
PhyloP100		0.083
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: rs874305; hg19: chr15-99196245;