rs1800975

Variant names:

• chr9-97697296-T-C
• rs1800975
• NM_000380.4:c.-4A>G

Your query was ambiguous. Multiple possible variants found:

• chr9-97697296-T-C
• chr9-97697296-T-A
• chr9-97697296-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000380.4(XPA):​c.-4A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 1,597,438 control chromosomes in the GnomAD database, including 352,759 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.69 (37112 hom., cov: 35)
  • Exomes 𝑓: 0.66 (315647 hom.)
• Consequence: XPA NM_000380.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.0190
• Publications: 200 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: Myriad Women’s Health, ClinGen, Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae)
• xeroderma pigmentosum

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 9-97697296-T-C is Benign according to our data. Variant chr9-97697296-T-C is described in ClinVar as Benign. ClinVar VariationId is 190206.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000380.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XPA	NM_000380.4	MANE Select	c.-4A>G		5_prime_UTR	Exon 1 of 6	NP_000371.1	P23025
	XPA	NM_001354975.2		c.-1153A>G		5_prime_UTR	Exon 1 of 6	NP_001341904.1
	XPA	NR_027302.2		n.45A>G		non_coding_transcript_exon	Exon 1 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XPA	ENST00000375128.5	TSL:1 MANE Select	c.-4A>G		5_prime_UTR	Exon 1 of 6	ENSP00000364270.5	P23025
	XPA	ENST00000905837.1		c.-4A>G		5_prime_UTR	Exon 1 of 4	ENSP00000575896.1
	XPA	ENST00000905836.1		c.-4A>G		5_prime_UTR	Exon 1 of 3	ENSP00000575895.1

Frequencies

GnomAD3 genomes AF: 0.692 AC: 105257 AN: 152098 Hom.: 37056 Cov.: 35

Gnomad AFR AF: 0.804

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.666

Gnomad ASJ AF: 0.632

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.682

GnomAD2 exomes AF: 0.632 AC: 140577 AN: 222442 AF XY: 0.627

Gnomad AFR exome AF: 0.804

Gnomad AMR exome AF: 0.628

Gnomad ASJ exome AF: 0.628

Gnomad EAS exome AF: 0.503

Gnomad FIN exome AF: 0.640

Gnomad NFE exome AF: 0.661

Gnomad OTH exome AF: 0.661

GnomAD4 exome AF: 0.659 AC: 951992 AN: 1445222 Hom.: 315647 Cov.: 80 AF XY: 0.654 AC XY: 470708 AN XY: 719532

African (AFR) AF: 0.807 AC: 26809 AN: 33240

American (AMR) AF: 0.637 AC: 28448 AN: 44626

Ashkenazi Jewish (ASJ) AF: 0.627 AC: 16326 AN: 26048

East Asian (EAS) AF: 0.504 AC: 19973 AN: 39600

South Asian (SAS) AF: 0.534 AC: 46039 AN: 86146

European-Finnish (FIN) AF: 0.639 AC: 24721 AN: 38672

Middle Eastern (MID) AF: 0.693 AC: 3865 AN: 5576

European-Non Finnish (NFE) AF: 0.672 AC: 746413 AN: 1111134

Other (OTH) AF: 0.655 AC: 39398 AN: 60180

GnomAD4 genome AF: 0.692 AC: 105373 AN: 152216 Hom.: 37112 Cov.: 35 AF XY: 0.687 AC XY: 51166 AN XY: 74434

African (AFR) AF: 0.805 AC: 33429 AN: 41552

American (AMR) AF: 0.666 AC: 10190 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.632 AC: 2194 AN: 3472

East Asian (EAS) AF: 0.513 AC: 2644 AN: 5158

South Asian (SAS) AF: 0.521 AC: 2516 AN: 4832

European-Finnish (FIN) AF: 0.638 AC: 6767 AN: 10608

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.669 AC: 45460 AN: 67978

Other (OTH) AF: 0.683 AC: 1444 AN: 2114

Alfa AF: 0.675 Hom.: 82136

Bravo AF: 0.701

Asia WGS AF: 0.535 AC: 1858 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	not specified (3)
-	-	2	Xeroderma pigmentosum group A (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.9
DANN	Benign	0.70
PhyloP100		-0.019
PromoterAI		-0.11	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1800975; hg19: chr9-100459578; COSMIC: COSV64305139; COSMIC: COSV64305139;