rs11949301

Variant names:

• chr5-83209334-C-A
• rs11949301
• NM_003401.5:c.745+4413C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-83209334-C-A
• chr5-83209334-C-G
• chr5-83209334-C-T

Variant summary

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

The NM_003401.5(XRCC4):​c.745+4413C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 151,882 control chromosomes in the GnomAD database, including 34,004 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 0.66 (34004 hom., cov: 31)
• Consequence: XRCC4 NM_003401.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.546
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XRCC4	NM_003401.5	c.745+4413C>A		intron_variant	Intron 6 of 7	ENST00000396027.9	NP_003392.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XRCC4	ENST00000396027.9	c.745+4413C>A		intron_variant	Intron 6 of 7	5	NM_003401.5	ENSP00000379344.4

Frequencies

GnomAD3 genomes AF: 0.660 AC: 100137 AN: 151764 Hom.: 33943 Cov.: 31

Gnomad AFR AF: 0.767

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.735

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.963

Gnomad SAS AF: 0.637

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.664

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

GnomAD4 genome AF: 0.660 AC: 100262 AN: 151882 Hom.: 34004 Cov.: 31 AF XY: 0.661 AC XY: 49082 AN XY: 74230

African (AFR) AF: 0.767 AC: 31811 AN: 41468

American (AMR) AF: 0.736 AC: 11212 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.678 AC: 2350 AN: 3466

East Asian (EAS) AF: 0.963 AC: 4977 AN: 5170

South Asian (SAS) AF: 0.638 AC: 3078 AN: 4826

European-Finnish (FIN) AF: 0.542 AC: 5706 AN: 10520

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.576 AC: 39077 AN: 67872

Other (OTH) AF: 0.668 AC: 1409 AN: 2110

Alfa AF: 0.606 Hom.: 14547

Bravo AF: 0.684

Asia WGS AF: 0.798 AC: 2777 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.74
DANN	Benign	0.16
PhyloP100		-0.55
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs11949301; hg19: chr5-82505153;