rs112591281

Variant names:

• chr2-219076447-T-C
• rs112591281
• NM_024782.3:c.834A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-219076447-T-C
• chr2-219076447-T-G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_024782.3(NHEJ1):​c.834A>G​(p.Ser278Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S278S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 30)
• Consequence: NHEJ1 NM_024782.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.445
• Publications: 0 publications found

Genes affected

NHEJ1 (HGNC:25737): (non-homologous end joining factor 1) Double-strand breaks in DNA result from genotoxic stresses and are among the most damaging of DNA lesions. This gene encodes a DNA repair factor essential for the nonhomologous end-joining pathway, which preferentially mediates repair of double-stranded breaks. Mutations in this gene cause different kinds of severe combined immunodeficiency disorders. [provided by RefSeq, Jul 2008]

NHEJ1 Gene-Disease associations (from GenCC):

• Cernunnos-XLF deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)

ENSG00000280537 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_addAF=-0.31866).
• BP7: Synonymous conserved (PhyloP=0.445 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NHEJ1	NM_024782.3	c.834A>G	p.Ser278Ser	synonymous_variant	Exon 8 of 8	ENST00000356853.10	NP_079058.1
NHEJ1	NM_001377499.1	c.849A>G	p.Ser283Ser	synonymous_variant	Exon 8 of 8		NP_001364428.1
NHEJ1	NM_001377498.1	c.834A>G	p.Ser278Ser	synonymous_variant	Exon 8 of 8		NP_001364427.1
NHEJ1	NR_165304.1	n.1012A>G		non_coding_transcript_exon_variant	Exon 9 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NHEJ1	ENST00000356853.10	c.834A>G	p.Ser278Ser	synonymous_variant	Exon 8 of 8	1	NM_024782.3	ENSP00000349313.5
ENSG00000280537	ENST00000318673.6	n.*1956A>G		non_coding_transcript_exon_variant	Exon 17 of 17	2		ENSP00000320919.3
ENSG00000280537	ENST00000318673.6	n.*1956A>G		3_prime_UTR_variant	Exon 17 of 17	2		ENSP00000320919.3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	14
DANN	Benign	0.89
Eigen	Benign	-0.052
Eigen_PC	Benign	-0.048
FATHMM_MKL	Benign	0.48	N
PhyloP100		0.45
GERP RS		3.7
Mutation Taster		=31/69	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs112591281; hg19: chr2-219941169;