dbSNP rs1009728: IGFBP4:c.350-30T>C (chr17-40452955-T-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001552.3(IGFBP4):c.350-30T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 1,450,950 control chromosomes in the GnomAD database, including 73,456 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. There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.30 ( 7072 hom., cov: 31)

Exomes 𝑓: 0.31 ( 66384 hom. )

Consequence

IGFBP4
NM_001552.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.974

Publications

12 publications found

Variant links:

Genes affected

IGFBP4 (HGNC:5473): (insulin like growth factor binding protein 4) This gene is a member of the insulin-like growth factor binding protein (IGFBP) family and encodes a protein with an IGFBP domain and a thyroglobulin type-I domain. The protein binds both insulin-like growth factors (IGFs) I and II and circulates in the plasma in both glycosylated and non-glycosylated forms. Binding of this protein prolongs the half-life of the IGFs and alters their interaction with cell surface receptors. [provided by RefSeq, Jul 2008]

IGFBP4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGFBP4	NM_001552.3 link	c.350-30T>C		intron_variant	Intron 1 of 3	ENST00000269593.5	NP_001543.2	P22692-1A0A024R1U8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGFBP4	ENST00000269593.5 link	c.350-30T>C		intron_variant	Intron 1 of 3	1	NM_001552.3	ENSP00000269593.4		P22692-1

Frequencies

GnomAD3 genomes

AF:

0.295

AC:

44853

AN:

151890

Hom.:

7061

Cov.:

show subpopulations

Gnomad AFR

AF:

0.212

Gnomad AMI

AF:

0.304

Gnomad AMR

AF:

0.301

Gnomad ASJ

AF:

0.413

Gnomad EAS

AF:

0.527

Gnomad SAS

AF:

0.416

Gnomad FIN

AF:

0.307

Gnomad MID

AF:

0.468

Gnomad NFE

AF:

0.308

Gnomad OTH

AF:

0.361

GnomAD2 exomes

AF:

0.325

AC:

53028

AN:

163000

AF XY:

0.334

show subpopulations

Gnomad AFR exome

AF:

0.214

Gnomad AMR exome

AF:

0.242

Gnomad ASJ exome

AF:

0.419

Gnomad EAS exome

AF:

0.520

Gnomad FIN exome

AF:

0.306

Gnomad NFE exome

AF:

0.314

Gnomad OTH exome

AF:

0.346

GnomAD4 exome

AF:

0.314

AC:

407295

AN:

1298942

Hom.:

66384

Cov.:

AF XY:

0.318

AC XY:

201655

AN XY:

634964

show subpopulations

African (AFR)

AF:

0.207

AC:

5719

AN:

27642

American (AMR)

AF:

0.258

AC:

7055

AN:

27384

Ashkenazi Jewish (ASJ)

AF:

0.414

AC:

8358

AN:

20186

East Asian (EAS)

AF:

0.518

AC:

16674

AN:

32198

South Asian (SAS)

AF:

0.416

AC:

25986

AN:

62420

European-Finnish (FIN)

AF:

0.303

AC:

14819

AN:

48888

Middle Eastern (MID)

AF:

0.461

AC:

2394

AN:

5198

European-Non Finnish (NFE)

AF:

0.302

AC:

308831

AN:

1021926

Other (OTH)

AF:

0.329

AC:

17459

AN:

53100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

11818

23636

35455

47273

59091

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10838

21676

32514

43352

54190

<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:

0.295

AC:

44894

AN:

152008

Hom.:

7072

Cov.:

AF XY:

0.298

AC XY:

22173

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.212

AC:

8791

AN:

41474

American (AMR)

AF:

0.301

AC:

4598

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.413

AC:

1431

AN:

3468

East Asian (EAS)

AF:

0.528

AC:

2714

AN:

5140

South Asian (SAS)

AF:

0.416

AC:

2005

AN:

4820

European-Finnish (FIN)

AF:

0.307

AC:

3245

AN:

10566

Middle Eastern (MID)

AF:

0.463

AC:

136

AN:

294

European-Non Finnish (NFE)

AF:

0.308

AC:

20924

AN:

67950

Other (OTH)

AF:

0.366

AC:

773

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1581

3162

4742

6323

7904

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

462

924

1386

1848

2310

<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:

0.311

Hom.:

6271

Bravo

AF:

0.291

Asia WGS

AF:

0.483

AC:

1679

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.55

PhyloP100

0.97

BranchPoint Hunter

6.0

Mutation Taster

=100/0

polymorphism (auto)

(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

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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