Variant 22-41621350-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBA1

The NM_001469.5(XRCC6):c.-16+5G>A variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0153 in 173,790 control chromosomes in the GnomAD database, including 75 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 Benign (★).

Frequency

Genomes: 𝑓 0.017 ( 75 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 0 hom. )

Consequence

XRCC6
NM_001469.5 splice_donor_5th_base, intron

Scores

Splicing: ADA: 0.9527

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.02

Variant links:

Genes affected

XRCC6 (HGNC:4055): (X-ray repair cross complementing 6) The p70/p80 autoantigen is a nuclear complex consisting of two subunits with molecular masses of approximately 70 and 80 kDa. The complex functions as a single-stranded DNA-dependent ATP-dependent helicase. The complex may be involved in the repair of nonhomologous DNA ends such as that required for double-strand break repair, transposition, and V(D)J recombination. High levels of autoantibodies to p70 and p80 have been found in some patients with systemic lupus erythematosus. [provided by RefSeq, Jul 2008]

XRCC6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 22-41621350-G-A is Benign according to our data. Variant chr22-41621350-G-A is described in ClinVar as [Benign]. Clinvar id is 1249874.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XRCC6	NM_001469.5 linkuse as main transcript	c.-16+5G>A		splice_donor_5th_base_variant, intron_variant		ENST00000360079.8	NP_001460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XRCC6	ENST00000360079.8 linkuse as main transcript	c.-16+5G>A		splice_donor_5th_base_variant, intron_variant		1	NM_001469.5	ENSP00000353192	P1	P12956-1

Frequencies

GnomAD3 genomes

AF:

0.0172

AC:

2625

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0595

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00673

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.0144

GnomAD4 exome

AF:

0.00116

AC:

AN:

21462

Hom.:

Cov.:

AF XY:

0.000968

AC XY:

AN XY:

11358

show subpopulations

Gnomad4 AFR exome

AF:

0.0481

Gnomad4 AMR exome

AF:

0.00485

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000960

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00255

GnomAD4 genome

AF:

0.0173

AC:

2630

AN:

152328

Hom.:

Cov.:

AF XY:

0.0158

AC XY:

1175

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0594

Gnomad4 AMR

AF:

0.00673

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000382

Gnomad4 OTH

AF:

0.0142

Alfa

AF:

0.00827

Hom.:

Bravo

AF:

0.0198

Asia WGS

AF:

0.00462

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 21, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.86

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.95

dbscSNV1_RF

Benign

0.60

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

Publications

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over