dbSNP rs3176757: XPA:c.772+713C>T (chr9-97674776-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The XM_006717278.2(XPA):c.772+713C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 379,068 control chromosomes in the GnomAD database, including 8,981 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 0.18 ( 2745 hom., cov: 33)

Exomes 𝑓: 0.22 ( 6236 hom. )

Consequence

XPA
XM_006717278.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.01

Publications

13 publications found

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]

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

XPA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XPA	NM_000380.4 link	c.*663C>T		downstream_gene_variant		ENST00000375128.5	NP_000371.1	P23025

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XPA	ENST00000375128.5 link	c.*663C>T		downstream_gene_variant		1	NM_000380.4	ENSP00000364270.5		P23025
XPA	ENST00000462523.5 link	n.*921C>T		downstream_gene_variant		5		ENSP00000433006.1		F2Z2T2

Frequencies

GnomAD3 genomes

AF:

0.178

AC:

27061

AN:

152024

Hom.:

2747

Cov.:

show subpopulations

Gnomad AFR

AF:

0.108

Gnomad AMI

AF:

0.322

Gnomad AMR

AF:

0.135

Gnomad ASJ

AF:

0.174

Gnomad EAS

AF:

0.245

Gnomad SAS

AF:

0.358

Gnomad FIN

AF:

0.262

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.198

Gnomad OTH

AF:

0.179

GnomAD4 exome

AF:

0.220

AC:

49819

AN:

226926

Hom.:

6236

AF XY:

0.233

AC XY:

28539

AN XY:

122596

show subpopulations

African (AFR)

AF:

0.102

AC:

624

AN:

6088

American (AMR)

AF:

0.110

AC:

1266

AN:

11554

Ashkenazi Jewish (ASJ)

AF:

0.170

AC:

1044

AN:

6124

East Asian (EAS)

AF:

0.222

AC:

3094

AN:

13920

South Asian (SAS)

AF:

0.348

AC:

14085

AN:

40526

European-Finnish (FIN)

AF:

0.250

AC:

2148

AN:

8594

Middle Eastern (MID)

AF:

0.208

AC:

176

AN:

846

European-Non Finnish (NFE)

AF:

0.195

AC:

24854

AN:

127508

Other (OTH)

AF:

0.215

AC:

2528

AN:

11766

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1750

3501

5251

7002

8752

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

230

460

690

920

1150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.178

AC:

27061

AN:

152142

Hom.:

2745

Cov.:

AF XY:

0.183

AC XY:

13613

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.108

AC:

4482

AN:

41536

American (AMR)

AF:

0.135

AC:

2060

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.174

AC:

604

AN:

3468

East Asian (EAS)

AF:

0.245

AC:

1269

AN:

5172

South Asian (SAS)

AF:

0.357

AC:

1720

AN:

4812

European-Finnish (FIN)

AF:

0.262

AC:

2765

AN:

10560

Middle Eastern (MID)

AF:

0.190

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.198

AC:

13435

AN:

67996

Other (OTH)

AF:

0.179

AC:

378

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1122

2244

3366

4488

5610

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

310

620

930

1240

1550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.187

Hom.:

4883

Bravo

AF:

0.161

Asia WGS

AF:

0.302

AC:

1051

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.18

(source)

DANN

Benign

0.42

PhyloP100

-1.0

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over