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19-43543687-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_006297.3(XRCC1):c.1713G>A(p.Gly571=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0016 in 1,613,902 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0016 ( 5 hom. )

Consequence

XRCC1
NM_006297.3 splice_region, synonymous

Scores

2
Splicing: ADA: 0.0007974
2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.199
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.45).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 19-43543687-C-T is Benign according to our data. Variant chr19-43543687-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1675749.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.199 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
XRCC1NM_006297.3 linkuse as main transcriptc.1713G>A p.Gly571= splice_region_variant, synonymous_variant 16/17 ENST00000262887.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
XRCC1ENST00000262887.10 linkuse as main transcriptc.1713G>A p.Gly571= splice_region_variant, synonymous_variant 16/171 NM_006297.3 P1
XRCC1ENST00000543982.5 linkuse as main transcriptc.1620G>A p.Gly540= splice_region_variant, synonymous_variant 15/162

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00121
AC:
184
AN:
151972
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000508
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00160
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00207
Gnomad OTH
AF:
0.000959
GnomAD3 exomes
AF:
0.00125
AC:
313
AN:
251194
Hom.:
2
AF XY:
0.00125
AC XY:
170
AN XY:
135750
show subpopulations
Gnomad AFR exome
AF:
0.000431
Gnomad AMR exome
AF:
0.000145
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000490
Gnomad FIN exome
AF:
0.00157
Gnomad NFE exome
AF:
0.00215
Gnomad OTH exome
AF:
0.00131
GnomAD4 exome
AF:
0.00164
AC:
2391
AN:
1461812
Hom.:
5
Cov.:
34
AF XY:
0.00163
AC XY:
1182
AN XY:
727216
show subpopulations
Gnomad4 AFR exome
AF:
0.000299
Gnomad4 AMR exome
AF:
0.000157
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000441
Gnomad4 FIN exome
AF:
0.00206
Gnomad4 NFE exome
AF:
0.00191
Gnomad4 OTH exome
AF:
0.00151
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00121
AC:
184
AN:
152090
Hom.:
0
Cov.:
31
AF XY:
0.000995
AC XY:
74
AN XY:
74354
show subpopulations
Gnomad4 AFR
AF:
0.000506
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00160
Gnomad4 NFE
AF:
0.00207
Gnomad4 OTH
AF:
0.000949
Alfa
AF:
0.00178
Hom.:
1
Bravo
AF:
0.00105
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenFeb 01, 2024XRCC1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.45
Cadd
Benign
3.3
Dann
Benign
0.61
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00080
dbscSNV1_RF
Benign
0.11
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2307182; hg19: chr19-44047839; API