chr19-43553124-G-A

Variant names:

• chr19-43553124-G-A
• rs1799780
• NM_006297.3:c.602-33C>T

Variant summary

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

The NM_006297.3(XRCC1):​c.602-33C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.052 in 1,544,636 control chromosomes in the GnomAD database, including 2,457 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency:
  • Genomes: 𝑓 0.051 (264 hom., cov: 31)
  • Exomes 𝑓: 0.052 (2193 hom.)
• Consequence: XRCC1 NM_006297.3 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -1.03
• Publications: 6 publications found

Genes affected

XRCC1 (HGNC:12828): (X-ray repair cross complementing 1) The protein encoded by this gene is involved in the efficient repair of DNA single-strand breaks formed by exposure to ionizing radiation and alkylating agents. This protein interacts with DNA ligase III, polymerase beta and poly (ADP-ribose) polymerase to participate in the base excision repair pathway. It may play a role in DNA processing during meiogenesis and recombination in germ cells. A rare microsatellite polymorphism in this gene is associated with cancer in patients of varying radiosensitivity. [provided by RefSeq, Jul 2008]

XRCC1 Gene-Disease associations (from GenCC):

• head and neck cancer

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• spinocerebellar ataxia, autosomal recessive 26

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0889 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006297.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC1	NM_006297.3	MANE Select	c.602-33C>T		intron	N/A	NP_006288.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC1	ENST00000262887.10	TSL:1 MANE Select	c.602-33C>T		intron	N/A	ENSP00000262887.5
	XRCC1	ENST00000543982.5	TSL:2	c.509-33C>T		intron	N/A	ENSP00000443671.1
	XRCC1	ENST00000598165.5	TSL:3	c.623-33C>T		intron	N/A	ENSP00000470045.1

Frequencies

GnomAD3 genomes AF: 0.0512 AC: 7785 AN: 152076 Hom.: 264 Cov.: 31

Gnomad AFR AF: 0.0309

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0825

Gnomad ASJ AF: 0.0582

Gnomad EAS AF: 0.0957

Gnomad SAS AF: 0.0961

Gnomad FIN AF: 0.0706

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.0462

Gnomad OTH AF: 0.0592

GnomAD2 exomes AF: 0.0722 AC: 11425 AN: 158310 AF XY: 0.0723

Gnomad AFR exome AF: 0.0275

Gnomad AMR exome AF: 0.115

Gnomad ASJ exome AF: 0.0614

Gnomad EAS exome AF: 0.106

Gnomad FIN exome AF: 0.0757

Gnomad NFE exome AF: 0.0491

Gnomad OTH exome AF: 0.0753

GnomAD4 exome AF: 0.0521 AC: 72492 AN: 1392442 Hom.: 2193 Cov.: 30 AF XY: 0.0531 AC XY: 36475 AN XY: 687518

African (AFR) AF: 0.0273 AC: 862 AN: 31626

American (AMR) AF: 0.109 AC: 3909 AN: 35814

Ashkenazi Jewish (ASJ) AF: 0.0614 AC: 1540 AN: 25084

East Asian (EAS) AF: 0.0891 AC: 3222 AN: 36154

South Asian (SAS) AF: 0.0885 AC: 7013 AN: 79220

European-Finnish (FIN) AF: 0.0747 AC: 3670 AN: 49110

Middle Eastern (MID) AF: 0.110 AC: 452 AN: 4112

European-Non Finnish (NFE) AF: 0.0452 AC: 48512 AN: 1073616

Other (OTH) AF: 0.0574 AC: 3312 AN: 57706

GnomAD4 genome AF: 0.0511 AC: 7782 AN: 152194 Hom.: 264 Cov.: 31 AF XY: 0.0550 AC XY: 4094 AN XY: 74394

African (AFR) AF: 0.0308 AC: 1281 AN: 41544

American (AMR) AF: 0.0825 AC: 1261 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0582 AC: 202 AN: 3470

East Asian (EAS) AF: 0.0957 AC: 495 AN: 5170

South Asian (SAS) AF: 0.0962 AC: 463 AN: 4814

European-Finnish (FIN) AF: 0.0706 AC: 749 AN: 10602

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.0462 AC: 3139 AN: 67990

Other (OTH) AF: 0.0577 AC: 122 AN: 2116

Alfa AF: 0.0541 Hom.: 40

Bravo AF: 0.0526

Asia WGS AF: 0.0930 AC: 322 AN: 3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Laryngeal squamous cell carcinoma Other:1

Jun 16, 2022

Department Of Otolaryngology, First Affiliated Hospital Of Xinjiang Medical University

Significance: association

Review Status: no assertion criteria provided

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.1
DANN	Benign	0.65
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1799780; hg19: chr19-44057276;