15-98933816-G-A

Variant names:

• chr15-98933816-G-A
• rs12438493
• NM_000875.5:c.2957-1008G>A

Variant summary

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

The NM_000875.5(IGF1R):​c.2957-1008G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 151,444 control chromosomes in the GnomAD database, including 15,847 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 0.46 (15847 hom., cov: 31)
• Consequence: IGF1R NM_000875.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.51
• Publications: 1 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF1R	NM_000875.5	c.2957-1008G>A		intron_variant	Intron 15 of 20	ENST00000650285.1	NP_000866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGF1R	ENST00000650285.1	c.2957-1008G>A		intron_variant	Intron 15 of 20		NM_000875.5	ENSP00000497069.1
IGF1R	ENST00000560972.1	n.260-1500G>A		intron_variant	Intron 3 of 3	1
IGF1R	ENST00000649865.1	c.2954-1008G>A		intron_variant	Intron 15 of 20			ENSP00000496919.1

Frequencies

GnomAD3 genomes AF: 0.456 AC: 68999 AN: 151326 Hom.: 15838 Cov.: 31

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.397

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.428

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

GnomAD4 genome AF: 0.456 AC: 69049 AN: 151444 Hom.: 15847 Cov.: 31 AF XY: 0.451 AC XY: 33380 AN XY: 73994

African (AFR) AF: 0.522 AC: 21529 AN: 41254

American (AMR) AF: 0.403 AC: 6126 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 1618 AN: 3460

East Asian (EAS) AF: 0.335 AC: 1718 AN: 5124

South Asian (SAS) AF: 0.318 AC: 1524 AN: 4800

European-Finnish (FIN) AF: 0.417 AC: 4356 AN: 10458

Middle Eastern (MID) AF: 0.410 AC: 119 AN: 290

European-Non Finnish (NFE) AF: 0.454 AC: 30774 AN: 67842

Other (OTH) AF: 0.422 AC: 887 AN: 2100

Alfa AF: 0.362 Hom.: 1280

Bravo AF: 0.460

Asia WGS AF: 0.340 AC: 1181 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.23
DANN	Benign	0.72
PhyloP100		-2.5
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: rs12438493; hg19: chr15-99477045;