rs4134860

chr19-7621521-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.558

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XAB2	NM_020196.3	c.1618-224T>C		intron_variant		ENST00000358368.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XAB2	ENST00000358368.5	c.1618-224T>C		intron_variant		1	NM_020196.3	P1
XAB2	ENST00000595288.5	n.3024T>C		non_coding_transcript_exon_variant	8/11	2
XAB2	ENST00000596134.1	n.13T>C		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26334 AN: 151894 Hom.: 2324 Cov.: 32

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.: 4 AF XY: 0.197 AC XY: 43465 AN XY: 220972

Gnomad4 AFR exome AF: 0.134

Gnomad4 AMR exome AF: 0.116

Gnomad4 ASJ exome AF: 0.168

Gnomad4 EAS exome AF: 0.201

Gnomad4 SAS exome AF: 0.221

Gnomad4 FIN exome AF: 0.217

Gnomad4 NFE exome AF: 0.198

Gnomad4 OTH exome AF: 0.192

GnomAD4 genome AF: 0.173 AC: 26359 AN: 152012 Hom.: 2332 Cov.: 32 AF XY: 0.174 AC XY: 12937 AN XY: 74320

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.191

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.225

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.179

Alfa AF: 0.181 Hom.: 471

Bravo AF: 0.162

Asia WGS AF: 0.199 AC: 691 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	3.7
Dann	Benign	0.69

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

LitVar

Other links and lift over

dbSNP: rs4134860; hg19: chr19-7686407;