rs4134819

Positions:

• chr19-7628345-C-T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.283

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=-0.83).
• 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/exons	MANE	Protein	UniProt
XAB2	NM_020196.3	c.52-47G>A		intron_variant		ENST00000358368.5	NP_064581.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XAB2	ENST00000358368.5	c.52-47G>A		intron_variant		1	NM_020196.3	ENSP00000351137.3

Frequencies

GnomAD3 genomes AF: 0.0724 AC: 11012 AN: 152042 Hom.: 1049 Cov.: 32

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

GnomAD3 exomes AF: 0.0777 AC: 19319 AN: 248772 Hom.: 2522 AF XY: 0.0723 AC XY: 9756 AN XY: 134898

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 SAS exome AF: 0.0793

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.: 31 AF XY: 0.0363 AC XY: 26343 AN XY: 725924

Gnomad4 AFR exome AF: 0.127

Gnomad4 AMR exome AF: 0.0931

Gnomad4 ASJ exome AF: 0.00990

Gnomad4 EAS exome AF: 0.505

Gnomad4 SAS exome AF: 0.0757

Gnomad4 FIN exome AF: 0.0638

Gnomad4 NFE exome AF: 0.00927

Gnomad4 OTH exome AF: 0.0520

GnomAD4 genome AF: 0.0725 AC: 11028 AN: 152160 Hom.: 1051 Cov.: 32 AF XY: 0.0787 AC XY: 5849 AN XY: 74362

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.0908

Gnomad4 ASJ AF: 0.0107

Gnomad4 EAS AF: 0.480

Gnomad4 SAS AF: 0.0932

Gnomad4 FIN AF: 0.0716

Gnomad4 NFE AF: 0.0111

Gnomad4 OTH AF: 0.0563

Alfa AF: 0.0224 Hom.: 206

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
DANN	Benign	0.67

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

LitVar

Other links and lift over

dbSNP: rs4134819; hg19: chr19-7693231; COSMIC: COSV60697540; COSMIC: COSV60697540;