dbSNP rs1815009: IGF1R:c.*4000C>T (chr15-98961442-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000875.5(IGF1R):c.*4000C>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 0.671 in 233,136 control chromosomes in the GnomAD database, including 53,938 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.65 ( 33620 hom., cov: 33)

Exomes 𝑓: 0.70 ( 20318 hom. )

Consequence

IGF1R
NM_000875.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0300

Publications

20 publications found

Variant links:

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 links:

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

SYNM-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 15-98961442-C-T is Benign according to our data. Variant chr15-98961442-C-T is described in ClinVar as Benign. ClinVar VariationId is 317570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.747 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.*4000C>T		3_prime_UTR	Exon 21 of 21	NP_000866.1	P08069
	IGF1R	NM_001291858.2		c.*4000C>T		3_prime_UTR	Exon 21 of 21	NP_001278787.1	C9J5X1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IGF1R	ENST00000650285.1	MANE Select	c.*4000C>T	3_prime_UTR	Exon 21 of 21	ENSP00000497069.1	P08069
IGF1R	ENST00000649865.1		c.*4000C>T	3_prime_UTR	Exon 21 of 21	ENSP00000496919.1	C9J5X1
SYNM-AS1	ENST00000559468.1	TSL:4	n.348+4547G>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.653

AC:

99292

AN:

151946

Hom.:

33608

Cov.:

show subpopulations

Gnomad AFR

AF:

0.473

Gnomad AMI

AF:

0.578

Gnomad AMR

AF:

0.629

Gnomad ASJ

AF:

0.709

Gnomad EAS

AF:

0.533

Gnomad SAS

AF:

0.680

Gnomad FIN

AF:

0.789

Gnomad MID

AF:

0.620

Gnomad NFE

AF:

0.753

Gnomad OTH

AF:

0.666

GnomAD4 exome

AF:

0.703

AC:

56997

AN:

81072

Hom.:

20318

Cov.:

AF XY:

0.705

AC XY:

26301

AN XY:

37282

show subpopulations

African (AFR)

AF:

0.473

AC:

1839

AN:

3888

American (AMR)

AF:

0.633

AC:

1575

AN:

2490

Ashkenazi Jewish (ASJ)

AF:

0.703

AC:

3596

AN:

5116

East Asian (EAS)

AF:

0.596

AC:

6792

AN:

11392

South Asian (SAS)

AF:

0.714

AC:

501

AN:

702

European-Finnish (FIN)

AF:

0.804

AC:

209

AN:

260

Middle Eastern (MID)

AF:

0.693

AC:

341

AN:

492

European-Non Finnish (NFE)

AF:

0.749

AC:

37439

AN:

49962

Other (OTH)

AF:

0.695

AC:

4705

AN:

6770

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

904

1808

2711

3615

4519

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

122

244

366

488

610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.653

AC:

99340

AN:

152064

Hom.:

33620

Cov.:

AF XY:

0.652

AC XY:

48436

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.473

AC:

19577

AN:

41422

American (AMR)

AF:

0.629

AC:

9614

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.709

AC:

2460

AN:

3468

East Asian (EAS)

AF:

0.533

AC:

2754

AN:

5170

South Asian (SAS)

AF:

0.681

AC:

3283

AN:

4824

European-Finnish (FIN)

AF:

0.789

AC:

8362

AN:

10600

Middle Eastern (MID)

AF:

0.629

AC:

185

AN:

294

European-Non Finnish (NFE)

AF:

0.753

AC:

51172

AN:

67986

Other (OTH)

AF:

0.668

AC:

1406

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1688

3376

5063

6751

8439

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

800

1600

2400

3200

4000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.714

Hom.:

50396

Bravo

AF:

0.633

Asia WGS

AF:

0.620

AC:

2155

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Growth delay due to insulin-like growth factor I resistance (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

5.3

(source)

DANN

Benign

0.74

PhyloP100

-0.030

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over