chr12-102402244-A-T

Variant names:

Variant summary

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

The NM_000618.5(IGF1):c.*263T>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 0.027 in 227,346 control chromosomes in the GnomAD database, including 93 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 60 hom., cov: 32)

Exomes 𝑓: 0.026 ( 33 hom. )

Consequence

IGF1
NM_000618.5 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.577

Publications

0 publications found

Variant links:

Genes affected

IGF1 (HGNC:5464): (insulin like growth factor 1) The protein encoded by this gene is similar to insulin in function and structure and is a member of a family of proteins involved in mediating growth and development. The encoded protein is processed from a precursor, bound by a specific receptor, and secreted. Defects in this gene are a cause of insulin-like growth factor I deficiency. Alternative splicing results in multiple transcript variants encoding different isoforms that may undergo similar processing to generate mature protein. [provided by RefSeq, Sep 2015]

IGF1 links:

HELLPAR (HGNC:43984): (HELLP associated long non-coding RNA)

HELLPAR links:

LINC02456 (HGNC:53389): (long intergenic non-protein coding RNA 2456)

LINC02456 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=-0.88).

BP6

Variant 12-102402244-A-T is Benign according to our data. Variant chr12-102402244-A-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 306905.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF1	NM_000618.5 link	c.*263T>A		3_prime_UTR_variant	Exon 4 of 4	ENST00000337514.11	NP_000609.1	P05019-2Q5U743Q59GC5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGF1	ENST00000337514.11 link	c.*263T>A		3_prime_UTR_variant	Exon 4 of 4	1	NM_000618.5	ENSP00000337612.7		P05019-2

Frequencies

GnomAD3 genomes

AF:

0.0274

AC:

4043

AN:

147580

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0201

Gnomad AMI

AF:

0.00120

Gnomad AMR

AF:

0.0252

Gnomad ASJ

AF:

0.0804

Gnomad EAS

AF:

0.0173

Gnomad SAS

AF:

0.0587

Gnomad FIN

AF:

0.0153

Gnomad MID

AF:

0.0449

Gnomad NFE

AF:

0.0301

Gnomad OTH

AF:

0.0270

GnomAD4 exome

AF:

0.0262

AC:

2088

AN:

79674

Hom.:

Cov.:

AF XY:

0.0272

AC XY:

1199

AN XY:

44146

show subpopulations

African (AFR)

AF:

0.0134

AC:

AN:

1872

American (AMR)

AF:

0.0284

AC:

114

AN:

4012

Ashkenazi Jewish (ASJ)

AF:

0.0495

AC:

103

AN:

2080

East Asian (EAS)

AF:

0.0171

AC:

AN:

4550

South Asian (SAS)

AF:

0.0485

AC:

427

AN:

8806

European-Finnish (FIN)

AF:

0.0108

AC:

AN:

2596

Middle Eastern (MID)

AF:

0.0432

AC:

AN:

324

European-Non Finnish (NFE)

AF:

0.0232

AC:

1187

AN:

51220

Other (OTH)

AF:

0.0266

AC:

112

AN:

4214

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

160

241

321

401

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.0274

AC:

4045

AN:

147672

Hom.:

Cov.:

AF XY:

0.0261

AC XY:

1882

AN XY:

72004

show subpopulations

African (AFR)

AF:

0.0201

AC:

812

AN:

40318

American (AMR)

AF:

0.0253

AC:

378

AN:

14946

Ashkenazi Jewish (ASJ)

AF:

0.0804

AC:

275

AN:

3422

East Asian (EAS)

AF:

0.0175

AC:

AN:

5142

South Asian (SAS)

AF:

0.0587

AC:

278

AN:

4734

European-Finnish (FIN)

AF:

0.0153

AC:

142

AN:

9294

Middle Eastern (MID)

AF:

0.0414

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0300

AC:

2002

AN:

66642

Other (OTH)

AF:

0.0268

AC:

AN:

2054

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

173

346

519

692

865

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

192

240

<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:

0.00380

Hom.:

Bravo

AF:

0.0273

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Growth delay due to insulin-like growth factor type 1 deficiency

Benign:2

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

not specified

Benign:2

Apr 27, 2018

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 25, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: 1KG: 3.5% (174/5008) total chromosomes, associated with insulin-like growth factor deficiency, sib does not carry variant -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.27

(source)

DANN

Benign

0.51

PhyloP100

0.58

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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over