dbSNP rs7454: IGFBP1:c.*316C>G (chr7-45893407-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_000596.4(IGFBP1):c.*316C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0348 in 153,260 control chromosomes in the GnomAD database, including 135 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.035 ( 135 hom., cov: 33)

Exomes 𝑓: 0.025 ( 0 hom. )

Consequence

IGFBP1
NM_000596.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.751

Publications

6 publications found

Variant links:

Genes affected

IGFBP1 (HGNC:5469): (insulin like growth factor binding protein 1) This gene is a member of the insulin-like growth factor binding protein (IGFBP) family and encodes a protein with an IGFBP N-terminal domain and a thyroglobulin type-I domain. The encoded protein, mainly expressed in the liver, circulates in the plasma and binds both insulin-like growth factors (IGFs) I and II, prolonging their half-lives and altering their interaction with cell surface receptors. This protein is important in cell migration and metabolism. Low levels of this protein may be associated with impaired glucose tolerance, vascular disease and hypertension in human patients. [provided by RefSeq, Aug 2017]

IGFBP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0348 (5302/152232) while in subpopulation AMR AF = 0.0492 (752/15292). AF 95% confidence interval is 0.0463. There are 135 homozygotes in GnomAd4. There are 2615 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 135 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGFBP1	NM_000596.4 link	c.*316C>G		3_prime_UTR_variant	Exon 4 of 4	ENST00000275525.8	NP_000587.1	P08833

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
IGFBP1	ENST00000275525.8 link	c.*316C>G	3_prime_UTR_variant	Exon 4 of 4	1	NM_000596.4	ENSP00000275525.3	P08833
IGFBP1	ENST00000457280.5 link	c.*316C>G	3_prime_UTR_variant	Exon 4 of 4	5		ENSP00000413511.1	C9JXF9
IGFBP1	ENST00000468955.1 link	c.*316C>G	3_prime_UTR_variant	Exon 3 of 3	5		ENSP00000417069.1	C9J6H2

Frequencies

GnomAD3 genomes

AF:

0.0348

AC:

5293

AN:

152114

Hom.:

131

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0126

Gnomad AMI

AF:

0.0428

Gnomad AMR

AF:

0.0484

Gnomad ASJ

AF:

0.00980

Gnomad EAS

AF:

0.00251

Gnomad SAS

AF:

0.0396

Gnomad FIN

AF:

0.0555

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0458

Gnomad OTH

AF:

0.0239

GnomAD4 exome

AF:

0.0253

AC:

AN:

1028

Hom.:

Cov.:

AF XY:

0.0189

AC XY:

AN XY:

582

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.0323

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0288

AC:

AN:

764

Other (OTH)

AF:

0.0417

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.0348

AC:

5302

AN:

152232

Hom.:

135

Cov.:

AF XY:

0.0351

AC XY:

2615

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.0126

AC:

525

AN:

41534

American (AMR)

AF:

0.0492

AC:

752

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00980

AC:

AN:

3470

East Asian (EAS)

AF:

0.00251

AC:

AN:

5176

South Asian (SAS)

AF:

0.0392

AC:

189

AN:

4822

European-Finnish (FIN)

AF:

0.0555

AC:

588

AN:

10602

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0457

AC:

3110

AN:

68016

Other (OTH)

AF:

0.0237

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

273

547

820

1094

1367

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

192

256

320

<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:

0.0391

Hom.:

Bravo

AF:

0.0352

Asia WGS

AF:

0.0270

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.2

(source)

DANN

Benign

0.56

PhyloP100

0.75

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

0.97

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over