Genetic Variant XAB2:c.52-47G>A (chr19-7628345-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_020196.3(XAB2):c.52-47G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0392 in 1,611,456 control chromosomes in the GnomAD database, including 7,437 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 0.072 ( 1051 hom., cov: 32)

Exomes 𝑓: 0.036 ( 6386 hom. )

Consequence

XAB2
NM_020196.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.283

Publications

9 publications found

Variant links:

Genes affected

XAB2 (HGNC:14089): (XPA binding protein 2) Involved in mRNA splicing, via spliceosome; transcription, DNA-templated; and transcription-coupled nucleotide-excision repair. Located in nucleoplasm. Part of U2-type catalytic step 2 spliceosome. [provided by Alliance of Genome Resources, Apr 2022]

XAB2 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 (EAS) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020196.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XAB2	NM_020196.3	MANE Select	c.52-47G>A		intron	N/A	NP_064581.2	Q9HCS7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
XAB2	ENST00000358368.5	TSL:1 MANE Select	c.52-47G>A	intron	N/A	ENSP00000351137.3	Q9HCS7
XAB2	ENST00000925818.1		c.52-47G>A	intron	N/A	ENSP00000595877.1
XAB2	ENST00000925815.1		c.52-47G>A	intron	N/A	ENSP00000595874.1

Frequencies

GnomAD3 genomes

AF:

0.0724

AC:

11012

AN:

152042

Hom.:

1049

Cov.:

show subpopulations

Gnomad AFR

AF:

0.121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0907

Gnomad ASJ

AF:

0.0107

Gnomad EAS

AF:

0.481

Gnomad SAS

AF:

0.0929

Gnomad FIN

AF:

0.0716

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0111

Gnomad OTH

AF:

0.0565

GnomAD2 exomes

AF:

0.0777

AC:

19319

AN:

248772

AF XY:

0.0723

show subpopulations

Gnomad AFR exome

AF:

0.128

Gnomad AMR exome

AF:

0.0934

Gnomad ASJ exome

AF:

0.0105

Gnomad EAS exome

AF:

0.473

Gnomad FIN exome

AF:

0.0652

Gnomad NFE exome

AF:

0.0110

Gnomad OTH exome

AF:

0.0430

GnomAD4 exome

AF:

0.0357

AC:

52091

AN:

1459296

Hom.:

6386

Cov.:

AF XY:

0.0363

AC XY:

26343

AN XY:

725924

show subpopulations

African (AFR)

AF:

0.127

AC:

4240

AN:

33436

American (AMR)

AF:

0.0931

AC:

4154

AN:

44630

Ashkenazi Jewish (ASJ)

AF:

0.00990

AC:

258

AN:

26064

East Asian (EAS)

AF:

0.505

AC:

20033

AN:

39646

South Asian (SAS)

AF:

0.0757

AC:

6510

AN:

86020

European-Finnish (FIN)

AF:

0.0638

AC:

3376

AN:

52874

Middle Eastern (MID)

AF:

0.0177

AC:

AN:

5140

European-Non Finnish (NFE)

AF:

0.00927

AC:

10297

AN:

1111224

Other (OTH)

AF:

0.0520

AC:

3132

AN:

60262

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

2045

4090

6135

8180

10225

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

762

1524

2286

3048

3810

<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:

0.0725

AC:

11028

AN:

152160

Hom.:

1051

Cov.:

AF XY:

0.0787

AC XY:

5849

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.121

AC:

5034

AN:

41470

American (AMR)

AF:

0.0908

AC:

1389

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0107

AC:

AN:

3472

East Asian (EAS)

AF:

0.480

AC:

2480

AN:

5162

South Asian (SAS)

AF:

0.0932

AC:

450

AN:

4828

European-Finnish (FIN)

AF:

0.0716

AC:

759

AN:

10602

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0111

AC:

754

AN:

68014

Other (OTH)

AF:

0.0563

AC:

119

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

445

891

1336

1782

2227

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

240

360

480

600

<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:

0.0343

Hom.:

1528

Bravo

AF:

0.0763

Asia WGS

AF:

0.242

AC:

840

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.4

(source)

DANN

Benign

0.67

PhyloP100

0.28

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over