dbSNP rs2276983: HMGXB3:c.2731-63G>A (chr5-150045403-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_014983.3(HMGXB3):c.2731-63G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.794 in 1,308,540 control chromosomes in the GnomAD database, including 415,227 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 0.83 ( 53493 hom., cov: 31)

Exomes 𝑓: 0.79 ( 361734 hom. )

Consequence

HMGXB3
NM_014983.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.492

Publications

5 publications found

Variant links:

Genes affected

HMGXB3 (HGNC:28982): (HMG-box containing 3) This gene is one of the non-canonical high mobility group (HMG) genes. The encoded protein contains an HMG-box domain found in DNA binding proteins such as transcription factors and chromosomal proteins. [provided by RefSeq, Aug 2011]

HMGXB3 Gene-Disease associations (from GenCC):

Tourette syndrome
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

HMGXB3 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=-0.86).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMGXB3	NM_014983.3 link	c.2731-63G>A		intron_variant	Intron 15 of 19	ENST00000502717.6	NP_055798.3	Q12766Q562E5
HMGXB3	NM_001366501.2 link	c.2233-63G>A		intron_variant	Intron 14 of 18		NP_001353430.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
HMGXB3	ENST00000502717.6 link	c.2731-63G>A	intron_variant	Intron 15 of 19	1	NM_014983.3	ENSP00000421917.1	Q12766
HMGXB3	ENST00000613459.4 link	c.3469-63G>A	intron_variant	Intron 16 of 20	5		ENSP00000479027.1	A0A8C8PVR7
HMGXB3	ENST00000503427.5 link	c.2635-63G>A	intron_variant	Intron 16 of 20	5		ENSP00000422231.1	E9PEK0
HMGXB3	ENST00000514469.1 link	n.*285-63G>A	intron_variant	Intron 5 of 6	5		ENSP00000426631.1	H0YAC2

Frequencies

GnomAD3 genomes

AF:

0.835

AC:

126935

AN:

152048

Hom.:

53440

Cov.:

show subpopulations

Gnomad AFR

AF:

0.956

Gnomad AMI

AF:

0.775

Gnomad AMR

AF:

0.790

Gnomad ASJ

AF:

0.814

Gnomad EAS

AF:

0.699

Gnomad SAS

AF:

0.699

Gnomad FIN

AF:

0.822

Gnomad MID

AF:

0.696

Gnomad NFE

AF:

0.796

Gnomad OTH

AF:

0.802

GnomAD4 exome

AF:

0.789

AC:

912576

AN:

1156372

Hom.:

361734

AF XY:

0.786

AC XY:

456203

AN XY:

580582

show subpopulations

African (AFR)

AF:

0.960

AC:

25726

AN:

26790

American (AMR)

AF:

0.783

AC:

27553

AN:

35206

Ashkenazi Jewish (ASJ)

AF:

0.814

AC:

19085

AN:

23458

East Asian (EAS)

AF:

0.642

AC:

22162

AN:

34500

South Asian (SAS)

AF:

0.697

AC:

51372

AN:

73678

European-Finnish (FIN)

AF:

0.828

AC:

40326

AN:

48706

Middle Eastern (MID)

AF:

0.749

AC:

3906

AN:

5214

European-Non Finnish (NFE)

AF:

0.795

AC:

682842

AN:

858996

Other (OTH)

AF:

0.795

AC:

39604

AN:

49824

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

10095

20190

30285

40380

50475

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14820

29640

44460

59280

74100

<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:

0.835

AC:

127043

AN:

152168

Hom.:

53493

Cov.:

AF XY:

0.832

AC XY:

61903

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.956

AC:

39723

AN:

41536

American (AMR)

AF:

0.790

AC:

12082

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.814

AC:

2826

AN:

3472

East Asian (EAS)

AF:

0.699

AC:

3611

AN:

5166

South Asian (SAS)

AF:

0.699

AC:

3367

AN:

4816

European-Finnish (FIN)

AF:

0.822

AC:

8704

AN:

10590

Middle Eastern (MID)

AF:

0.680

AC:

200

AN:

294

European-Non Finnish (NFE)

AF:

0.796

AC:

54139

AN:

67982

Other (OTH)

AF:

0.799

AC:

1686

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1029

2058

3086

4115

5144

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

880

1760

2640

3520

4400

<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:

0.843

Hom.:

9377

Bravo

AF:

0.838

Asia WGS

AF:

0.723

AC:

2520

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.083

(source)

DANN

Benign

0.25

PhyloP100

-0.49

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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