dbSNP rs2307187: XRCC1:c.-1C>T (chr19-43575459-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP6BA1

The NM_006297.3(XRCC1):c.-1C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.015 in 1,612,136 control chromosomes in the GnomAD database, including 271 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.021 ( 48 hom., cov: 32)

Exomes 𝑓: 0.014 ( 223 hom. )

Consequence

XRCC1
NM_006297.3 5_prime_UTR

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.46

Publications

9 publications found

Variant links:

COSMIC-nc: COSV53450509

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 links:

ENSG00000268361 (HGNC:):

ENSG00000268361 links:

PINLYP (HGNC:44206): (phospholipase A2 inhibitor and LY6/PLAUR domain containing) Predicted to enable phospholipase inhibitor activity. Predicted to be involved in negative regulation of catalytic activity. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

PINLYP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 19-43575459-G-A is Benign according to our data. Variant chr19-43575459-G-A is described in ClinVar as Benign. ClinVar VariationId is 3060460.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0512 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC1	NM_006297.3	MANE Select	c.-1C>T		5_prime_UTR	Exon 1 of 17	NP_006288.2	P18887

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
XRCC1	ENST00000262887.10	TSL:1 MANE Select	c.-1C>T	5_prime_UTR	Exon 1 of 17	ENSP00000262887.5	P18887
ENSG00000268361	ENST00000594374.1	TSL:3	c.169-14439C>T	intron	N/A	ENSP00000472698.1	M0R2N6
XRCC1	ENST00000953258.1		c.-1C>T	5_prime_UTR	Exon 1 of 17	ENSP00000623317.1

Frequencies

GnomAD3 genomes

AF:

0.0214

AC:

3256

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0364

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.0285

Gnomad ASJ

AF:

0.0222

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0168

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0154

Gnomad OTH

AF:

0.0234

GnomAD2 exomes

AF:

0.0148

AC:

3686

AN:

249656

AF XY:

0.0151

show subpopulations

Gnomad AFR exome

AF:

0.0371

Gnomad AMR exome

AF:

0.0138

Gnomad ASJ exome

AF:

0.0251

Gnomad EAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.00158

Gnomad NFE exome

AF:

0.0150

Gnomad OTH exome

AF:

0.0241

GnomAD4 exome

AF:

0.0143

AC:

20942

AN:

1459824

Hom.:

223

Cov.:

AF XY:

0.0144

AC XY:

10432

AN XY:

726060

show subpopulations

African (AFR)

AF:

0.0421

AC:

1407

AN:

33438

American (AMR)

AF:

0.0158

AC:

706

AN:

44596

Ashkenazi Jewish (ASJ)

AF:

0.0257

AC:

671

AN:

26088

East Asian (EAS)

AF:

0.0000505

AC:

AN:

39626

South Asian (SAS)

AF:

0.0172

AC:

1477

AN:

86064

European-Finnish (FIN)

AF:

0.00210

AC:

112

AN:

53380

Middle Eastern (MID)

AF:

0.0563

AC:

324

AN:

5758

European-Non Finnish (NFE)

AF:

0.0136

AC:

15057

AN:

1110622

Other (OTH)

AF:

0.0197

AC:

1186

AN:

60252

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

986

1972

2959

3945

4931

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

564

1128

1692

2256

2820

<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:

0.0214

AC:

3262

AN:

152312

Hom.:

Cov.:

AF XY:

0.0210

AC XY:

1565

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.0364

AC:

1515

AN:

41568

American (AMR)

AF:

0.0285

AC:

436

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0222

AC:

AN:

3472

East Asian (EAS)

AF:

0.000578

AC:

AN:

5190

South Asian (SAS)

AF:

0.0170

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00151

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0155

AC:

1051

AN:

68022

Other (OTH)

AF:

0.0232

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

164

328

493

657

821

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<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:

0.0197

Hom.:

Bravo

AF:

0.0249

Asia WGS

AF:

0.00895

AC:

AN:

3478

EpiCase

AF:

0.0177

EpiControl

AF:

0.0177

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

XRCC1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Benign

0.89

PhyloP100

2.5

PromoterAI

-0.041

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Mutation Taster

=298/2

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over