rs2808667

Variant summary

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

The NM_000380.4(XPA):​c.673+4399A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.957 in 152,302 control chromosomes in the GnomAD database, including 69,839 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 0.96 ( 69839 hom., cov: 32)

Consequence

XPA
NM_000380.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.53
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.93).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.98 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
XPANM_000380.4 linkuse as main transcriptc.673+4399A>G intron_variant ENST00000375128.5 NP_000371.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
XPAENST00000375128.5 linkuse as main transcriptc.673+4399A>G intron_variant 1 NM_000380.4 ENSP00000364270 P1
XPAENST00000462523.5 linkuse as main transcriptc.*109+1676A>G intron_variant, NMD_transcript_variant 5 ENSP00000433006

Frequencies

GnomAD3 genomes
AF:
0.957
AC:
145707
AN:
152184
Hom.:
69778
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.988
Gnomad AMI
AF:
0.924
Gnomad AMR
AF:
0.969
Gnomad ASJ
AF:
0.958
Gnomad EAS
AF:
0.999
Gnomad SAS
AF:
0.985
Gnomad FIN
AF:
0.958
Gnomad MID
AF:
0.975
Gnomad NFE
AF:
0.931
Gnomad OTH
AF:
0.962
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.957
AC:
145827
AN:
152302
Hom.:
69839
Cov.:
32
AF XY:
0.960
AC XY:
71510
AN XY:
74476
show subpopulations
Gnomad4 AFR
AF:
0.989
Gnomad4 AMR
AF:
0.969
Gnomad4 ASJ
AF:
0.958
Gnomad4 EAS
AF:
0.999
Gnomad4 SAS
AF:
0.985
Gnomad4 FIN
AF:
0.958
Gnomad4 NFE
AF:
0.931
Gnomad4 OTH
AF:
0.962
Alfa
AF:
0.939
Hom.:
93076
Bravo
AF:
0.960
Asia WGS
AF:
0.994
AC:
3457
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.93
CADD
Benign
0.65
DANN
Benign
0.46

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: rs2808667; hg19: chr9-100442806; API