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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XRCC4	XM_017009827.3	c.894-7515A>G		intron_variant	Intron 7 of 8		XP_016865316.1
XRCC4	XM_047417695.1	c.894-7515A>G		intron_variant	Intron 7 of 8		XP_047273651.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

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 v4.3

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;