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: G2P, ClinGen, Genomics England PanelApp, 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XPA	XM_006717278.2	c.772+1176C>T		intron_variant	Intron 6 of 6		XP_006717341.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

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 v4.3

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;