rs8030950

Variant names:

• chr15-98860792-C-A
• rs8030950
• NM_000875.5:c.641-30533C>A

Your query was ambiguous. Multiple possible variants found:

• chr15-98860792-C-A
• chr15-98860792-C-G
• chr15-98860792-C-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.641-30533C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 151,968 control chromosomes in the GnomAD database, including 10,574 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 0.35 (10574 hom., cov: 32)
• Consequence: IGF1R NM_000875.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 11 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, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.782 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF1R	NM_000875.5	MANE Select	c.641-30533C>A		intron	N/A	NP_000866.1	P08069
	IGF1R	NM_001291858.2		c.641-30533C>A		intron	N/A	NP_001278787.1	C9J5X1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF1R	ENST00000650285.1	MANE Select	c.641-30533C>A		intron	N/A	ENSP00000497069.1	P08069
	IGF1R	ENST00000559925.5	TSL:1	n.641-30533C>A		intron	N/A
	IGF1R	ENST00000649865.1		c.641-30533C>A		intron	N/A	ENSP00000496919.1	C9J5X1

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53288 AN: 151850 Hom.: 10527 Cov.: 32

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.258

Gnomad EAS AF: 0.802

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.287

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.364

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

GnomAD4 genome AF: 0.351 AC: 53394 AN: 151968 Hom.: 10574 Cov.: 32 AF XY: 0.362 AC XY: 26854 AN XY: 74252

African (AFR) AF: 0.388 AC: 16075 AN: 41428

American (AMR) AF: 0.490 AC: 7488 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.258 AC: 892 AN: 3464

East Asian (EAS) AF: 0.802 AC: 4141 AN: 5164

South Asian (SAS) AF: 0.451 AC: 2171 AN: 4814

European-Finnish (FIN) AF: 0.297 AC: 3141 AN: 10562

Middle Eastern (MID) AF: 0.288 AC: 84 AN: 292

European-Non Finnish (NFE) AF: 0.269 AC: 18294 AN: 67946

Other (OTH) AF: 0.372 AC: 785 AN: 2110

Alfa AF: 0.300 Hom.: 3079

Bravo AF: 0.368

Asia WGS AF: 0.586 AC: 2037 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.90
DANN	Benign	0.64
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs8030950; hg19: chr15-99404021;