rs6436114

Positions:

• chr2-219138112-T-G

Variant summary

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

The NM_024782.3(NHEJ1):​c.588+8568A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.721 in 151,980 control chromosomes in the GnomAD database, including 39,978 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 0.72 (39978 hom., cov: 31)
• Consequence: NHEJ1 NM_024782.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.588

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NHEJ1	NM_024782.3	c.588+8568A>C		intron_variant		ENST00000356853.10	NP_079058.1
NHEJ1	NM_001377498.1	c.588+8568A>C		intron_variant			NP_001364427.1
NHEJ1	NM_001377499.1	c.588+8568A>C		intron_variant			NP_001364428.1
NHEJ1	NR_165304.1	n.684+8568A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NHEJ1	ENST00000356853.10	c.588+8568A>C		intron_variant		1	NM_024782.3	ENSP00000349313	P4

Frequencies

GnomAD3 genomes AF: 0.721 AC: 109563 AN: 151862 Hom.: 39960 Cov.: 31

Gnomad AFR AF: 0.706

Gnomad AMI AF: 0.654

Gnomad AMR AF: 0.641

Gnomad ASJ AF: 0.701

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.621

Gnomad FIN AF: 0.820

Gnomad MID AF: 0.634

Gnomad NFE AF: 0.764

Gnomad OTH AF: 0.695

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

GnomAD4 genome AF: 0.721 AC: 109630 AN: 151980 Hom.: 39978 Cov.: 31 AF XY: 0.719 AC XY: 53375 AN XY: 74272

Gnomad4 AFR AF: 0.706

Gnomad4 AMR AF: 0.641

Gnomad4 ASJ AF: 0.701

Gnomad4 EAS AF: 0.453

Gnomad4 SAS AF: 0.622

Gnomad4 FIN AF: 0.820

Gnomad4 NFE AF: 0.765

Gnomad4 OTH AF: 0.689

Alfa AF: 0.738 Hom.: 19970

Bravo AF: 0.706

Asia WGS AF: 0.496 AC: 1726 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	1.5
DANN	Benign	0.72

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

Publications

LitVar

Other links and lift over

dbSNP: rs6436114; hg19: chr2-220002834;