rs794078

Positions:

• chr19-7620957-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000358368.5(XAB2):​c.1860C>T​(p.Thr620=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 1,582,630 control chromosomes in the GnomAD database, including 33,659 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 0.18 (2550 hom., cov: 33)
  • Exomes 𝑓: 0.21 (31109 hom.)
• Consequence: XAB2 ENST00000358368.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0210

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP7: Synonymous conserved (PhyloP=-0.021 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XAB2	NM_020196.3	c.1860C>T	p.Thr620=	synonymous_variant	14/19	ENST00000358368.5	NP_064581.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XAB2	ENST00000358368.5	c.1860C>T	p.Thr620=	synonymous_variant	14/19	1	NM_020196.3	ENSP00000351137	P1
XAB2	ENST00000595288.5	n.3588C>T		non_coding_transcript_exon_variant	8/11	2
XAB2	ENST00000596134.1	n.479C>T		non_coding_transcript_exon_variant	2/2	2
XAB2	ENST00000600230.1	n.243C>T		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27033 AN: 152120 Hom.: 2551 Cov.: 33

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.177

GnomAD3 exomes AF: 0.177 AC: 34916 AN: 197120 Hom.: 3222 AF XY: 0.177 AC XY: 18719 AN XY: 105948

Gnomad AFR exome AF: 0.137

Gnomad AMR exome AF: 0.138

Gnomad ASJ exome AF: 0.168

Gnomad EAS exome AF: 0.126

Gnomad SAS exome AF: 0.134

Gnomad FIN exome AF: 0.194

Gnomad NFE exome AF: 0.213

Gnomad OTH exome AF: 0.195

GnomAD4 exome AF: 0.205 AC: 293510 AN: 1430392 Hom.: 31109 Cov.: 51 AF XY: 0.203 AC XY: 143841 AN XY: 708416

Gnomad4 AFR exome AF: 0.137

Gnomad4 AMR exome AF: 0.145

Gnomad4 ASJ exome AF: 0.168

Gnomad4 EAS exome AF: 0.135

Gnomad4 SAS exome AF: 0.132

Gnomad4 FIN exome AF: 0.197

Gnomad4 NFE exome AF: 0.219

Gnomad4 OTH exome AF: 0.197

GnomAD4 genome AF: 0.178 AC: 27045 AN: 152238 Hom.: 2550 Cov.: 33 AF XY: 0.175 AC XY: 13020 AN XY: 74434

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.185

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.175

Alfa AF: 0.200 Hom.: 5928

Bravo AF: 0.178

Asia WGS AF: 0.129 AC: 449 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.0
DANN	Benign	0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs794078; hg19: chr19-7685843; COSMIC: COSV50336838; COSMIC: COSV50336838;