rs2808676

Variant names:

• chr9-97674313-G-A
• rs2808676
• XM_006717278.2:c.772+1176C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_006717278.2(XPA):​c.772+1176C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 144,646 control chromosomes in the GnomAD database, including 2,700 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 0.19 (2700 hom., cov: 32)
• Consequence: XPA XM_006717278.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.252
• Publications: 1 publications found

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]

XPA Gene-Disease associations (from GenCC):

• xeroderma pigmentosum group A

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, ClinGen, G2P, Labcorp Genetics (formerly Invitae), Myriad Women’s Health
• xeroderma pigmentosum

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Variant Effect in Transcripts

 

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes AF: 0.193 AC: 27880 AN: 144554 Hom.: 2694 Cov.: 32

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.0427

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.193 AC: 27919 AN: 144646 Hom.: 2700 Cov.: 32 AF XY: 0.193 AC XY: 13622 AN XY: 70686

African (AFR) AF: 0.265 AC: 9176 AN: 34586

American (AMR) AF: 0.167 AC: 2503 AN: 14990

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 484 AN: 3472

East Asian (EAS) AF: 0.0426 AC: 216 AN: 5070

South Asian (SAS) AF: 0.148 AC: 709 AN: 4794

European-Finnish (FIN) AF: 0.222 AC: 2333 AN: 10494

Middle Eastern (MID) AF: 0.154 AC: 45 AN: 292

European-Non Finnish (NFE) AF: 0.175 AC: 11865 AN: 67972

Other (OTH) AF: 0.170 AC: 352 AN: 2066

Alfa AF: 0.179 Hom.: 342

Bravo AF: 0.181

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.4
DANN	Benign	0.52
PhyloP100		0.25

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2808676; hg19: chr9-100436595;