dbSNP rs6220: IGF1:c.*1770C>T (chr12-102400737-G-A) – 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_000618.5(IGF1):c.*1770C>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 0.669 in 151,930 control chromosomes in the GnomAD database, including 34,277 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.67 ( 34277 hom., cov: 31)

Failed GnomAD Quality Control

Consequence

IGF1
NM_000618.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.633

Publications

64 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=-0.9).

BP6

Variant 12-102400737-G-A is Benign according to our data. Variant chr12-102400737-G-A is described in ClinVar as Benign. ClinVar VariationId is 306892.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000618.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IGF1	NM_000618.5	MANE Select	c.*1770C>T	3_prime_UTR	Exon 4 of 4	NP_000609.1	Q5U743
IGF1	NM_001111283.3		c.*1804C>T	3_prime_UTR	Exon 5 of 5	NP_001104753.1	P05019-4
IGF1	NM_001414007.1		c.*1770C>T	3_prime_UTR	Exon 5 of 5	NP_001400936.1	Q5U743

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IGF1	ENST00000337514.11	TSL:1 MANE Select	c.*1770C>T	3_prime_UTR	Exon 4 of 4	ENSP00000337612.7	P05019-2
HELLPAR	ENST00000626826.1	TSL:6	n.203153G>A	non_coding_transcript_exon	Exon 1 of 1
LINC02456	ENST00000635615.1	TSL:5	n.450-22334G>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.669

AC:

101625

AN:

151812

Hom.:

34283

Cov.:

show subpopulations

Gnomad AFR

AF:

0.589

Gnomad AMI

AF:

0.849

Gnomad AMR

AF:

0.736

Gnomad ASJ

AF:

0.716

Gnomad EAS

AF:

0.555

Gnomad SAS

AF:

0.667

Gnomad FIN

AF:

0.658

Gnomad MID

AF:

0.715

Gnomad NFE

AF:

0.709

Gnomad OTH

AF:

0.678

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.669

AC:

101647

AN:

151930

Hom.:

34277

Cov.:

AF XY:

0.669

AC XY:

49690

AN XY:

74256

show subpopulations

African (AFR)

AF:

0.589

AC:

24384

AN:

41402

American (AMR)

AF:

0.736

AC:

11241

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.716

AC:

2486

AN:

3472

East Asian (EAS)

AF:

0.555

AC:

2869

AN:

5168

South Asian (SAS)

AF:

0.666

AC:

3191

AN:

4794

European-Finnish (FIN)

AF:

0.658

AC:

6935

AN:

10542

Middle Eastern (MID)

AF:

0.711

AC:

209

AN:

294

European-Non Finnish (NFE)

AF:

0.708

AC:

48140

AN:

67952

Other (OTH)

AF:

0.671

AC:

1418

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1707

3414

5120

6827

8534

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

808

1616

2424

3232

4040

<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:

0.704

Hom.:

41620

Bravo

AF:

0.670

Asia WGS

AF:

0.574

AC:

1989

AN:

3462

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

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

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.65

(source)

DANN

Benign

0.38

PhyloP100

0.63

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over