rs3743250

Variant names:

• chr15-98962087-C-T
• rs3743250
• NM_000875.5:c.*4645C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-98962087-C-T
• chr15-98962087-C-A
• chr15-98962087-C-G

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.*4645C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 233,124 control chromosomes in the GnomAD database, including 3,450 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1955 hom., cov: 33)
  • Exomes 𝑓: 0.18 (1495 hom.)
• Consequence: IGF1R NM_000875.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.35
• Publications: 8 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=-0.89).
• BP6: Variant 15-98962087-C-T is Benign according to our data. Variant chr15-98962087-C-T is described in ClinVar as Benign. ClinVar VariationId is 317588.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.386 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.*4645C>T		3_prime_UTR	Exon 21 of 21	NP_000866.1	P08069
	IGF1R	NM_001291858.2		c.*4645C>T		3_prime_UTR	Exon 21 of 21	NP_001278787.1	C9J5X1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF1R	ENST00000650285.1	MANE Select	c.*4645C>T		3_prime_UTR	Exon 21 of 21	ENSP00000497069.1	P08069
	IGF1R	ENST00000649865.1		c.*4645C>T		3_prime_UTR	Exon 21 of 21	ENSP00000496919.1	C9J5X1
	SYNM-AS1	ENST00000559468.1	TSL:4	n.348+3902G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22782 AN: 152036 Hom.: 1958 Cov.: 33

Gnomad AFR AF: 0.0952

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.156

GnomAD4 exome AF: 0.178 AC: 14386 AN: 80970 Hom.: 1495 Cov.: 0 AF XY: 0.176 AC XY: 6566 AN XY: 37228

African (AFR) AF: 0.0910 AC: 354 AN: 3892

American (AMR) AF: 0.196 AC: 491 AN: 2500

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 970 AN: 5124

East Asian (EAS) AF: 0.344 AC: 3921 AN: 11406

South Asian (SAS) AF: 0.195 AC: 137 AN: 702

European-Finnish (FIN) AF: 0.113 AC: 7 AN: 62

Middle Eastern (MID) AF: 0.163 AC: 80 AN: 492

European-Non Finnish (NFE) AF: 0.147 AC: 7344 AN: 50030

Other (OTH) AF: 0.160 AC: 1082 AN: 6762

GnomAD4 genome AF: 0.150 AC: 22777 AN: 152154 Hom.: 1955 Cov.: 33 AF XY: 0.155 AC XY: 11498 AN XY: 74388

African (AFR) AF: 0.0950 AC: 3942 AN: 41508

American (AMR) AF: 0.203 AC: 3098 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 640 AN: 3468

East Asian (EAS) AF: 0.400 AC: 2068 AN: 5168

South Asian (SAS) AF: 0.206 AC: 995 AN: 4830

European-Finnish (FIN) AF: 0.149 AC: 1582 AN: 10584

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9900 AN: 67990

Other (OTH) AF: 0.155 AC: 326 AN: 2106

Alfa AF: 0.139 Hom.: 558

Bravo AF: 0.151

Asia WGS AF: 0.253 AC: 879 AN: 3478

ClinVar

ClinVar submissions

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	-0.89
CADD	Benign	0.079
DANN	Benign	0.44
PhyloP100		-2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs3743250; hg19: chr15-99505316; COSMIC: COSV51398070; COSMIC: COSV51398070;