Genetic Variant NM_020196.3:c.1618-224T>C (chr19-7621521-A-G) – 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.1618-224T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 574,912 control chromosomes in the GnomAD database, including 10,706 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 0.17 ( 2332 hom., cov: 32)

Exomes 𝑓: 0.19 ( 8374 hom. )

Consequence

XAB2
NM_020196.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.558

Publications

11 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=-0.89).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.215 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.1618-224T>C		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.1618-224T>C	intron	N/A	ENSP00000351137.3	Q9HCS7
XAB2	ENST00000925818.1		c.1648-224T>C	intron	N/A	ENSP00000595877.1
XAB2	ENST00000925815.1		c.1618-224T>C	intron	N/A	ENSP00000595874.1

Frequencies

GnomAD3 genomes

AF:

0.173

AC:

26334

AN:

151894

Hom.:

2324

Cov.:

show subpopulations

Gnomad AFR

AF:

0.132

Gnomad AMI

AF:

0.0934

Gnomad AMR

AF:

0.135

Gnomad ASJ

AF:

0.165

Gnomad EAS

AF:

0.191

Gnomad SAS

AF:

0.227

Gnomad FIN

AF:

0.225

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.195

Gnomad OTH

AF:

0.172

GnomAD4 exome

AF:

0.195

AC:

82416

AN:

422900

Hom.:

8374

Cov.:

AF XY:

0.197

AC XY:

43465

AN XY:

220972

show subpopulations

African (AFR)

AF:

0.134

AC:

1616

AN:

12062

American (AMR)

AF:

0.116

AC:

2013

AN:

17348

Ashkenazi Jewish (ASJ)

AF:

0.168

AC:

2190

AN:

13016

East Asian (EAS)

AF:

0.201

AC:

5956

AN:

29576

South Asian (SAS)

AF:

0.221

AC:

8950

AN:

40588

European-Finnish (FIN)

AF:

0.217

AC:

5982

AN:

27536

Middle Eastern (MID)

AF:

0.183

AC:

344

AN:

1878

European-Non Finnish (NFE)

AF:

0.198

AC:

50614

AN:

256194

Other (OTH)

AF:

0.192

AC:

4751

AN:

24702

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

3093

6186

9279

12372

15465

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

340

680

1020

1360

1700

<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:

0.173

AC:

26359

AN:

152012

Hom.:

2332

Cov.:

AF XY:

0.174

AC XY:

12937

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.132

AC:

5473

AN:

41466

American (AMR)

AF:

0.136

AC:

2070

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.165

AC:

572

AN:

3470

East Asian (EAS)

AF:

0.191

AC:

989

AN:

5166

South Asian (SAS)

AF:

0.226

AC:

1092

AN:

4834

European-Finnish (FIN)

AF:

0.225

AC:

2375

AN:

10574

Middle Eastern (MID)

AF:

0.190

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.195

AC:

13270

AN:

67916

Other (OTH)

AF:

0.179

AC:

377

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1181

2362

3542

4723

5904

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

298

596

894

1192

1490

<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:

0.179

Hom.:

479

Bravo

AF:

0.162

Asia WGS

AF:

0.199

AC:

691

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

3.7

(source)

DANN

Benign

0.69

PhyloP100

-0.56

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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