rs2805835

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000380.4(XPA):​c.673+2254G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0862 in 152,148 control chromosomes in the GnomAD database, including 731 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 0.086 ( 731 hom., cov: 32)

Consequence

XPA
NM_000380.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0320
Variant links:
Genes affected
XPA (HGNC:12814): (XPA, DNA damage recognition and repair factor) This gene encodes a zinc finger protein plays a central role in nucleotide excision repair (NER), a specialized type of DNA repair. NER is responsible for repair of UV radiation-induced photoproducts and DNA adducts induced by chemical carcinogens and chemotherapeutic drugs. The encoded protein interacts with DNA and several NER proteins, acting as a scaffold to assemble the NER incision complex at sites of DNA damage. Mutations in this gene cause Xeroderma pigmentosum complementation group A (XP-A), an autosomal recessive skin disorder featuring hypersensitivity to sunlight and increased risk for skin cancer. [provided by RefSeq, Aug 2017]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
XPANM_000380.4 linkuse as main transcriptc.673+2254G>C intron_variant ENST00000375128.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
XPAENST00000375128.5 linkuse as main transcriptc.673+2254G>C intron_variant 1 NM_000380.4 P1
XPAENST00000462523.5 linkuse as main transcriptc.674-239G>C intron_variant, NMD_transcript_variant 5

Frequencies

GnomAD3 genomes
AF:
0.0861
AC:
13096
AN:
152030
Hom.:
725
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0326
Gnomad AMI
AF:
0.127
Gnomad AMR
AF:
0.110
Gnomad ASJ
AF:
0.0716
Gnomad EAS
AF:
0.0425
Gnomad SAS
AF:
0.135
Gnomad FIN
AF:
0.142
Gnomad MID
AF:
0.0696
Gnomad NFE
AF:
0.105
Gnomad OTH
AF:
0.0818
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0862
AC:
13110
AN:
152148
Hom.:
731
Cov.:
32
AF XY:
0.0882
AC XY:
6559
AN XY:
74382
show subpopulations
Gnomad4 AFR
AF:
0.0325
Gnomad4 AMR
AF:
0.111
Gnomad4 ASJ
AF:
0.0716
Gnomad4 EAS
AF:
0.0424
Gnomad4 SAS
AF:
0.135
Gnomad4 FIN
AF:
0.142
Gnomad4 NFE
AF:
0.105
Gnomad4 OTH
AF:
0.0852
Alfa
AF:
0.0923
Hom.:
102
Bravo
AF:
0.0800
Asia WGS
AF:
0.114
AC:
396
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
CADD
Benign
10
DANN
Benign
0.71

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2805835; hg19: chr9-100444951; API