dbSNP rs4687554: ENSG00000243696:n.763A>G (chr3-52830119-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000513520.1(ENSG00000243696):n.763A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 346,970 control chromosomes in the GnomAD database, including 10,272 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 0.25 ( 4863 hom., cov: 34)

Exomes 𝑓: 0.22 ( 5409 hom. )

Consequence

ENSG00000243696
ENST00000513520.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0520

Publications

27 publications found

Variant links:

Genes affected

ENSG00000243696 (HGNC:):

ENSG00000243696 links:

ITIH4 (HGNC:6169): (inter-alpha-trypsin inhibitor heavy chain 4) The protein encoded by this gene is secreted into the blood, where it is cleaved by plasma kallikrein into two smaller forms. Expression of this gene has been detected only in liver, and it seems to be upregulated during surgical trauma. This gene is part of a cluster of similar genes on chromosome 3. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

ITIH4 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=-0.89).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITIH4	NM_002218.5 link	c.90+434A>G		intron_variant	Intron 1 of 23	ENST00000266041.9	NP_002209.2	Q14624-1B7ZKJ8B2RMS9
ITIH4	NM_001166449.2 link	c.90+434A>G		intron_variant	Intron 1 of 21		NP_001159921.1	Q14624-3B7ZKJ8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITIH4	ENST00000266041.9 link	c.90+434A>G		intron_variant	Intron 1 of 23	1	NM_002218.5	ENSP00000266041.4		Q14624-1
ENSG00000243696	ENST00000468472.1 link	n.*222+434A>G		intron_variant	Intron 6 of 23	2		ENSP00000422253.1		D6R8Y8

Frequencies

GnomAD3 genomes

AF:

0.246

AC:

37354

AN:

152102

Hom.:

4862

Cov.:

show subpopulations

Gnomad AFR

AF:

0.209

Gnomad AMI

AF:

0.402

Gnomad AMR

AF:

0.374

Gnomad ASJ

AF:

0.313

Gnomad EAS

AF:

0.321

Gnomad SAS

AF:

0.128

Gnomad FIN

AF:

0.257

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.234

Gnomad OTH

AF:

0.244

GnomAD4 exome

AF:

0.221

AC:

43083

AN:

194750

Hom.:

5409

Cov.:

AF XY:

0.207

AC XY:

22062

AN XY:

106616

show subpopulations

African (AFR)

AF:

0.213

AC:

1092

AN:

5134

American (AMR)

AF:

0.426

AC:

3962

AN:

9296

Ashkenazi Jewish (ASJ)

AF:

0.314

AC:

1392

AN:

4438

East Asian (EAS)

AF:

0.312

AC:

2494

AN:

7994

South Asian (SAS)

AF:

0.120

AC:

4917

AN:

41018

European-Finnish (FIN)

AF:

0.254

AC:

2217

AN:

8742

Middle Eastern (MID)

AF:

0.212

AC:

150

AN:

708

European-Non Finnish (NFE)

AF:

0.229

AC:

24749

AN:

108102

Other (OTH)

AF:

0.226

AC:

2110

AN:

9318

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1676

3351

5027

6702

8378

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

200

400

600

800

1000

<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:

0.246

AC:

37379

AN:

152220

Hom.:

4863

Cov.:

AF XY:

0.247

AC XY:

18422

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.209

AC:

8689

AN:

41556

American (AMR)

AF:

0.374

AC:

5718

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.313

AC:

1085

AN:

3472

East Asian (EAS)

AF:

0.321

AC:

1657

AN:

5166

South Asian (SAS)

AF:

0.128

AC:

620

AN:

4830

European-Finnish (FIN)

AF:

0.257

AC:

2725

AN:

10596

Middle Eastern (MID)

AF:

0.238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.234

AC:

15930

AN:

67994

Other (OTH)

AF:

0.246

AC:

520

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1474

2949

4423

5898

7372

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

374

748

1122

1496

1870

<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:

0.235

Hom.:

2875

Bravo

AF:

0.256

Asia WGS

AF:

0.237

AC:

823

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

4.7

(source)

DANN

Benign

0.44

PhyloP100

-0.052

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