chr5-83359290-C-T

Position:

• chr5-83359290-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_017009827.3(XRCC4):​c.894-10977C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 151,968 control chromosomes in the GnomAD database, including 7,523 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 0.26 (7523 hom., cov: 32)
• Consequence: XRCC4 XM_017009827.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.403

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XRCC4	XM_017009827.3	c.894-10977C>T		intron_variant			XP_016865316.1
XRCC4	XM_047417695.1	c.894-10977C>T		intron_variant			XP_047273651.1
		n.83359290C>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39160 AN: 151850 Hom.: 7485 Cov.: 32

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.681

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.236

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

GnomAD4 genome AF: 0.258 AC: 39244 AN: 151968 Hom.: 7523 Cov.: 32 AF XY: 0.262 AC XY: 19428 AN XY: 74286

Gnomad4 AFR AF: 0.480

Gnomad4 AMR AF: 0.313

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.681

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.240

Alfa AF: 0.189 Hom.: 554

Bravo AF: 0.286

Asia WGS AF: 0.402 AC: 1397 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.33

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9293337; hg19: chr5-82655109; COSMIC: COSV60160626;