rs1052483

Positions:

• chr2-219069626-G-T

Variant summary

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

The NM_024782.3(NHEJ1):​c.*6755C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,240 control chromosomes in the GnomAD database, including 1,349 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 0.13 (1349 hom., cov: 32)
  • Exomes 𝑓: 0.11 (0 hom.)
• Consequence: NHEJ1 NM_024782.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.655

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NHEJ1	NM_024782.3	c.*6755C>A		3_prime_UTR_variant	8/8	ENST00000356853.10	NP_079058.1
LOC124906120	XR_007088092.1	n.4482G>T		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NHEJ1	ENST00000356853.10	c.*6755C>A		3_prime_UTR_variant	8/8	1	NM_024782.3	ENSP00000349313	P4
	ENST00000666065.1	n.867G>T		non_coding_transcript_exon_variant	3/3

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19161 AN: 152102 Hom.: 1342 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.0617

Gnomad FIN AF: 0.0825

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0977

Gnomad OTH AF: 0.127

GnomAD4 exome AF: 0.111 AC: 2 AN: 18 Hom.: 0 Cov.: 0 AF XY: 0.0833 AC XY: 1 AN XY: 12

Gnomad4 AFR exome AF: 0.500

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.126 AC: 19196 AN: 152222 Hom.: 1349 Cov.: 32 AF XY: 0.124 AC XY: 9231 AN XY: 74442

Gnomad4 AFR AF: 0.199

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.145

Gnomad4 SAS AF: 0.0619

Gnomad4 FIN AF: 0.0825

Gnomad4 NFE AF: 0.0977

Gnomad4 OTH AF: 0.128

Alfa AF: 0.101 Hom.: 1856

Bravo AF: 0.134

Asia WGS AF: 0.129 AC: 448 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.9
DANN	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1052483; hg19: chr2-219934348;