dbSNP rs2535629: ITIH3:c.789+112G>A (chr3-52799203-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002217.4(ITIH3):c.789+112G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 1,380,636 control chromosomes in the GnomAD database, including 97,334 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 0.45 ( 17354 hom., cov: 33)

Exomes 𝑓: 0.35 ( 79980 hom. )

Consequence

ITIH3
NM_002217.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.906

Publications

74 publications found

Variant links:

Genes affected

ITIH3 (HGNC:6168): (inter-alpha-trypsin inhibitor heavy chain 3) This gene encodes the heavy chain subunit of the pre-alpha-trypsin inhibitor complex. This complex may stabilize the extracellular matrix through its ability to bind hyaluronic acid. Polymorphisms of this gene may be associated with increased risk for schizophrenia and major depressive disorder. This gene is present in an inter-alpha-trypsin inhibitor family gene cluster on chromosome 3. [provided by RefSeq, Jul 2015]

ITIH3 links:

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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=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITIH3	NM_002217.4 link	c.789+112G>A		intron_variant	Intron 7 of 21	ENST00000449956.3	NP_002208.3	Q06033-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITIH3	ENST00000449956.3 link	c.789+112G>A		intron_variant	Intron 7 of 21	1	NM_002217.4	ENSP00000415769.2		Q06033-1

Frequencies

GnomAD3 genomes

AF:

0.454

AC:

68989

AN:

151988

Hom.:

17325

Cov.:

show subpopulations

Gnomad AFR

AF:

0.681

Gnomad AMI

AF:

0.469

Gnomad AMR

AF:

0.484

Gnomad ASJ

AF:

0.378

Gnomad EAS

AF:

0.372

Gnomad SAS

AF:

0.312

Gnomad FIN

AF:

0.349

Gnomad MID

AF:

0.377

Gnomad NFE

AF:

0.347

Gnomad OTH

AF:

0.412

GnomAD4 exome

AF:

0.353

AC:

433425

AN:

1228530

Hom.:

79980

Cov.:

AF XY:

0.349

AC XY:

213158

AN XY:

610212

show subpopulations

African (AFR)

AF:

0.693

AC:

19940

AN:

28790

American (AMR)

AF:

0.519

AC:

18283

AN:

35248

Ashkenazi Jewish (ASJ)

AF:

0.393

AC:

8805

AN:

22416

East Asian (EAS)

AF:

0.419

AC:

14999

AN:

35764

South Asian (SAS)

AF:

0.303

AC:

21545

AN:

71142

European-Finnish (FIN)

AF:

0.352

AC:

16843

AN:

47880

Middle Eastern (MID)

AF:

0.390

AC:

1572

AN:

4032

European-Non Finnish (NFE)

AF:

0.336

AC:

312907

AN:

931022

Other (OTH)

AF:

0.355

AC:

18531

AN:

52236

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

14098

28196

42294

56392

70490

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9816

19632

29448

39264

49080

<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:

0.454

AC:

69070

AN:

152106

Hom.:

17354

Cov.:

AF XY:

0.453

AC XY:

33717

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.681

AC:

28261

AN:

41486

American (AMR)

AF:

0.484

AC:

7395

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.378

AC:

1312

AN:

3470

East Asian (EAS)

AF:

0.372

AC:

1920

AN:

5158

South Asian (SAS)

AF:

0.311

AC:

1501

AN:

4826

European-Finnish (FIN)

AF:

0.349

AC:

3703

AN:

10598

Middle Eastern (MID)

AF:

0.374

AC:

110

AN:

294

European-Non Finnish (NFE)

AF:

0.347

AC:

23567

AN:

67970

Other (OTH)

AF:

0.414

AC:

873

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1809

3618

5428

7237

9046

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

598

1196

1794

2392

2990

<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:

0.385

Hom.:

33248

Bravo

AF:

0.475

Asia WGS

AF:

0.378

AC:

1313

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.61

(source)

DANN

Benign

0.28

PhyloP100

-0.91

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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