rs10057194

Variant names:

• chr5-83362752-A-G
• rs10057194
• XM_017009827.3:c.894-7515A>G

Your query was ambiguous. Multiple possible variants found:

• chr5-83362752-A-G
• chr5-83362752-A-T

Variant summary

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

The XM_017009827.3(XRCC4):​c.894-7515A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,114 control chromosomes in the GnomAD database, including 3,339 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.15 (3339 hom., cov: 32)
• Consequence: XRCC4 XM_017009827.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 5 publications found

Genes affected

XRCC4 (HGNC:12831): (X-ray repair cross complementing 4) The protein encoded by this gene functions together with DNA ligase IV and the DNA-dependent protein kinase in the repair of DNA double-strand breaks. This protein plays a role in both non-homologous end joining and the completion of V(D)J recombination. Mutations in this gene can cause short stature, microcephaly, and endocrine dysfunction (SSMED). Alternate transcript variants such as NM_022406 are unlikely to be expressed in some individuals due to a polymorphism (rs1805377) in the last splice acceptor site. [provided by RefSeq, Oct 2019]

XRCC4 Gene-Disease associations (from GenCC):

• short stature, microcephaly, and endocrine dysfunction

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Laboratory for Molecular Medicine
• microcephalic primordial dwarfism-insulin resistance syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary nonpolyposis colon cancer

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Variant Effect in Transcripts

 

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23471 AN: 151996 Hom.: 3315 Cov.: 32

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.0879

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.0517

Gnomad FIN AF: 0.0640

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0521

Gnomad OTH AF: 0.125

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.155 AC: 23542 AN: 152114 Hom.: 3339 Cov.: 32 AF XY: 0.152 AC XY: 11314 AN XY: 74362

African (AFR) AF: 0.378 AC: 15657 AN: 41460

American (AMR) AF: 0.115 AC: 1755 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0879 AC: 305 AN: 3468

East Asian (EAS) AF: 0.199 AC: 1027 AN: 5170

South Asian (SAS) AF: 0.0516 AC: 249 AN: 4828

European-Finnish (FIN) AF: 0.0640 AC: 679 AN: 10612

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.0521 AC: 3543 AN: 67984

Other (OTH) AF: 0.127 AC: 268 AN: 2112

Alfa AF: 0.108 Hom.: 272

Bravo AF: 0.172

Asia WGS AF: 0.154 AC: 537 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.24
DANN	Benign	0.45
PhyloP100		-1.3

Splicing

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

Other links and lift over

dbSNP: rs10057194; hg19: chr5-82658571; COSMIC: COSV60160631;