Genetic Variant NM_020196.3: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:

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=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XAB2	NM_020196.3 link	c.52-47G>A		intron_variant	Intron 1 of 18	ENST00000358368.5	NP_064581.2	Q9HCS7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XAB2	ENST00000358368.5 link	c.52-47G>A		intron_variant	Intron 1 of 18	1	NM_020196.3	ENSP00000351137.3		Q9HCS7
XAB2	ENST00000595288.5 link	n.-75G>A		upstream_gene_variant		2

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over