rs794083

chr19-7626981-C-G

Variant summary

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

The NM_020196.3(XAB2):c.522+262G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 152,088 control chromosomes in the GnomAD database, including 29,717 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 0.62 (29717 hom., cov: 33)
• Consequence: XAB2 NM_020196.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0710

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XAB2	NM_020196.3	c.522+262G>C		intron_variant		ENST00000358368.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XAB2	ENST00000358368.5	c.522+262G>C		intron_variant		1	NM_020196.3	P1
XAB2	ENST00000595288.5	n.1028+262G>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.618 AC: 93964 AN: 151970 Hom.: 29678 Cov.: 33

Gnomad AFR AF: 0.719

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.345

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.604

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.618 AC: 94057 AN: 152088 Hom.: 29717 Cov.: 33 AF XY: 0.616 AC XY: 45790 AN XY: 74328

Gnomad4 AFR AF: 0.719

Gnomad4 AMR AF: 0.582

Gnomad4 ASJ AF: 0.491

Gnomad4 EAS AF: 0.344

Gnomad4 SAS AF: 0.466

Gnomad4 FIN AF: 0.657

Gnomad4 NFE AF: 0.597

Gnomad4 OTH AF: 0.607

Alfa AF: 0.613 Hom.: 3584

Bravo AF: 0.619

Asia WGS AF: 0.457 AC: 1590 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	3.2
Dann	Benign	0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs794083; hg19: chr19-7691867;