Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The ENST00000650285.1(IGF1R):c.15C>T(p.Ser5Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000549 in 1,598,454 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0032 ( 6 hom., cov: 32)

Exomes 𝑓: 0.00028 ( 0 hom. )

Consequence

IGF1R
ENST00000650285.1 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.991

Publications

3 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:

IRAIN (HGNC:50365): (IGF1R antisense imprinted non-protein coding RNA) This gene expresses a long non-coding RNA in antisense to the insulin-like growth factor type I receptor (IGF1R) gene. This transcript is imprinted and expressed from the paternal allele. It interacts with chromatin and may promote long-range DNA interactions that influence the regulation of gene expression. [provided by RefSeq, Nov 2015]

IRAIN links:

ENSG00000278022 (HGNC:):

ENSG00000278022 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 15-98649596-C-T is Benign according to our data. Variant chr15-98649596-C-T is described in ClinVar as Benign. ClinVar VariationId is 718201.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.991 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00322 (478/148374) while in subpopulation AFR AF = 0.0115 (457/39888). AF 95% confidence interval is 0.0106. There are 6 homozygotes in GnomAd4. There are 219 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 6 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000650285.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
IGF1R	NM_000875.5	MANE Select	c.15C>T	p.Ser5Ser	synonymous	Exon 1 of 21	NP_000866.1
IGF1R	NM_001291858.2		c.15C>T	p.Ser5Ser	synonymous	Exon 1 of 21	NP_001278787.1
IRAIN	NR_126453.2		n.1192G>A		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
IGF1R	ENST00000650285.1	MANE Select	c.15C>T	p.Ser5Ser	synonymous	Exon 1 of 21	ENSP00000497069.1
IGF1R	ENST00000559925.5	TSL:1	n.15C>T		non_coding_transcript_exon	Exon 1 of 10
IGF1R	ENST00000649865.1		c.15C>T	p.Ser5Ser	synonymous	Exon 1 of 21	ENSP00000496919.1

Frequencies

GnomAD3 genomes

AF:

0.00322

AC:

478

AN:

148308

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0115

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00121

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000210

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000978

GnomAD2 exomes

AF:

0.000817

AC:

201

AN:

246124

AF XY:

0.000561

show subpopulations

Gnomad AFR exome

AF:

0.0117

Gnomad AMR exome

AF:

0.000479

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000508

GnomAD4 exome

AF:

0.000276

AC:

400

AN:

1450080

Hom.:

Cov.:

AF XY:

0.000224

AC XY:

162

AN XY:

721962

show subpopulations

African (AFR)

AF:

0.00963

AC:

319

AN:

33116

American (AMR)

AF:

0.000587

AC:

AN:

44264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25972

East Asian (EAS)

AF:

0.00

AC:

AN:

39406

South Asian (SAS)

AF:

0.00

AC:

AN:

85652

European-Finnish (FIN)

AF:

0.0000381

AC:

AN:

52496

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5732

European-Non Finnish (NFE)

AF:

0.00000544

AC:

AN:

1103474

Other (OTH)

AF:

0.000784

AC:

AN:

59968

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.00322

AC:

478

AN:

148374

Hom.:

Cov.:

AF XY:

0.00303

AC XY:

219

AN XY:

72198

show subpopulations

African (AFR)

AF:

0.0115

AC:

457

AN:

39888

American (AMR)

AF:

0.00121

AC:

AN:

14904

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3454

East Asian (EAS)

AF:

0.00

AC:

AN:

5002

South Asian (SAS)

AF:

0.000211

AC:

AN:

4732

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67518

Other (OTH)

AF:

0.000968

AC:

AN:

2066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

102

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00129

Hom.:

Bravo

AF:

0.00378

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.95

PhyloP100

0.99

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over