rs3743251

Variant names:

• chr15-98960900-G-A
• rs3743251
• NM_000875.5:c.*3458G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-98960900-G-A
• chr15-98960900-G-C
• chr15-98960900-G-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.*3458G>A 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 233,166 control chromosomes in the GnomAD database, including 3,353 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1903 hom., cov: 33)
  • Exomes 𝑓: 0.18 (1450 hom.)
• Consequence: IGF1R NM_000875.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.118
• Publications: 10 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=-0.8).
• BP6: Variant 15-98960900-G-A is Benign according to our data. Variant chr15-98960900-G-A is described in ClinVar as Benign. ClinVar VariationId is 317557.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.366 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.*3458G>A		3_prime_UTR	Exon 21 of 21	NP_000866.1	P08069
	IGF1R	NM_001291858.2		c.*3458G>A		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.*3458G>A		3_prime_UTR	Exon 21 of 21	ENSP00000497069.1	P08069
	IGF1R	ENST00000649865.1		c.*3458G>A		3_prime_UTR	Exon 21 of 21	ENSP00000496919.1	C9J5X1
	SYNM-AS1	ENST00000559468.1	TSL:4	n.348+5089C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22753 AN: 151386 Hom.: 1906 Cov.: 33

Gnomad AFR AF: 0.0994

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.158

GnomAD4 exome AF: 0.176 AC: 14382 AN: 81670 Hom.: 1450 Cov.: 0 AF XY: 0.175 AC XY: 6590 AN XY: 37672

African (AFR) AF: 0.0949 AC: 370 AN: 3898

American (AMR) AF: 0.197 AC: 492 AN: 2498

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 982 AN: 5126

East Asian (EAS) AF: 0.336 AC: 3835 AN: 11414

South Asian (SAS) AF: 0.195 AC: 137 AN: 704

European-Finnish (FIN) AF: 0.101 AC: 49 AN: 484

Middle Eastern (MID) AF: 0.164 AC: 81 AN: 494

European-Non Finnish (NFE) AF: 0.146 AC: 7354 AN: 50274

Other (OTH) AF: 0.160 AC: 1082 AN: 6778

GnomAD4 genome AF: 0.150 AC: 22746 AN: 151496 Hom.: 1903 Cov.: 33 AF XY: 0.155 AC XY: 11481 AN XY: 74038

African (AFR) AF: 0.0992 AC: 4076 AN: 41108

American (AMR) AF: 0.203 AC: 3098 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 654 AN: 3468

East Asian (EAS) AF: 0.380 AC: 1946 AN: 5120

South Asian (SAS) AF: 0.201 AC: 965 AN: 4798

European-Finnish (FIN) AF: 0.150 AC: 1583 AN: 10550

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.145 AC: 9867 AN: 67912

Other (OTH) AF: 0.156 AC: 330 AN: 2110

Alfa AF: 0.145 Hom.: 2323

Bravo AF: 0.151

Asia WGS AF: 0.244 AC: 848 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	-0.80
CADD	Benign	3.2
DANN	Benign	0.60
PhyloP100		-0.12
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: rs3743251; hg19: chr15-99504129; COSMIC: COSV51269833; COSMIC: COSV51269833;