rs2654981

Variant names:

• chr15-98961900-C-G
• rs2654981
• NM_000875.5:c.*4458C>G

Your query was ambiguous. Multiple possible variants found:

• chr15-98961900-C-G
• chr15-98961900-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000875.5(IGF1R):​c.*4458C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 233,094 control chromosomes in the GnomAD database, including 24,571 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.45 (15498 hom., cov: 33)
  • Exomes 𝑓: 0.47 (9073 hom.)
• Consequence: IGF1R NM_000875.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.573
• Publications: 12 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]

SYNM-AS1 (HGNC:55421): (SYNM antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 15-98961900-C-G is Benign according to our data. Variant chr15-98961900-C-G is described in ClinVar as Benign. ClinVar VariationId is 317580.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.537 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.*4458C>G		3_prime_UTR	Exon 21 of 21	NP_000866.1
	IGF1R	NM_001291858.2		c.*4458C>G		3_prime_UTR	Exon 21 of 21	NP_001278787.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF1R	ENST00000650285.1	MANE Select	c.*4458C>G		3_prime_UTR	Exon 21 of 21	ENSP00000497069.1
	IGF1R	ENST00000649865.1		c.*4458C>G		3_prime_UTR	Exon 21 of 21	ENSP00000496919.1
	SYNM-AS1	ENST00000559468.1	TSL:4	n.348+4089G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67804 AN: 152004 Hom.: 15486 Cov.: 33

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.678

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.433

GnomAD4 exome AF: 0.470 AC: 38088 AN: 80972 Hom.: 9073 Cov.: 0 AF XY: 0.470 AC XY: 17487 AN XY: 37208

African (AFR) AF: 0.342 AC: 1333 AN: 3896

American (AMR) AF: 0.501 AC: 1252 AN: 2500

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 2218 AN: 5124

East Asian (EAS) AF: 0.526 AC: 6000 AN: 11402

South Asian (SAS) AF: 0.401 AC: 281 AN: 700

European-Finnish (FIN) AF: 0.391 AC: 25 AN: 64

Middle Eastern (MID) AF: 0.392 AC: 193 AN: 492

European-Non Finnish (NFE) AF: 0.475 AC: 23739 AN: 50020

Other (OTH) AF: 0.450 AC: 3047 AN: 6774

GnomAD4 genome AF: 0.446 AC: 67841 AN: 152122 Hom.: 15498 Cov.: 33 AF XY: 0.446 AC XY: 33177 AN XY: 74378

African (AFR) AF: 0.346 AC: 14370 AN: 41480

American (AMR) AF: 0.492 AC: 7518 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 1501 AN: 3470

East Asian (EAS) AF: 0.553 AC: 2867 AN: 5180

South Asian (SAS) AF: 0.402 AC: 1943 AN: 4832

European-Finnish (FIN) AF: 0.467 AC: 4939 AN: 10574

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.486 AC: 33056 AN: 67988

Other (OTH) AF: 0.430 AC: 909 AN: 2112

Alfa AF: 0.346 Hom.: 1074

Bravo AF: 0.446

Asia WGS AF: 0.479 AC: 1668 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Growth delay due to insulin-like growth factor I resistance (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.6
DANN	Benign	0.64
PhyloP100		0.57
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: rs2654981; hg19: chr15-99505129;