Variant chr2-219076505-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_024782.3(NHEJ1):c.826-50C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00344 in 1,460,644 control chromosomes in the GnomAD database, including 166 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 86 hom., cov: 30)

Exomes 𝑓: 0.0019 ( 80 hom. )

Consequence

NHEJ1
NM_024782.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0520

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 2-219076505-G-A is Benign according to our data. Variant chr2-219076505-G-A is described in ClinVar as [Benign]. Clinvar id is 1294277.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
NHEJ1	NM_024782.3 linkuse as main transcript	c.826-50C>T	intron_variant	ENST00000356853.10	NP_079058.1
NHEJ1	NM_001377498.1 linkuse as main transcript	c.826-50C>T	intron_variant		NP_001364427.1
NHEJ1	NM_001377499.1 linkuse as main transcript	c.841-50C>T	intron_variant		NP_001364428.1
NHEJ1	NR_165304.1 linkuse as main transcript	n.1004-50C>T	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NHEJ1	ENST00000356853.10 linkuse as main transcript	c.826-50C>T		intron_variant		1	NM_024782.3	ENSP00000349313	P4	Q9H9Q4-1

Frequencies

GnomAD3 genomes

AF:

0.0171

AC:

2568

AN:

150414

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0594

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00641

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000212

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000251

Gnomad OTH

AF:

0.0112

GnomAD3 exomes

AF:

0.00440

AC:

1031

AN:

234400

Hom.:

AF XY:

0.00315

AC XY:

401

AN XY:

127146

show subpopulations

Gnomad AFR exome

AF:

0.0604

Gnomad AMR exome

AF:

0.00290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000579

Gnomad SAS exome

AF:

0.000205

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000184

Gnomad OTH exome

AF:

0.00137

GnomAD4 exome

AF:

0.00187

AC:

2451

AN:

1310164

Hom.:

Cov.:

AF XY:

0.00158

AC XY:

1035

AN XY:

654934

show subpopulations

Gnomad4 AFR exome

AF:

0.0635

Gnomad4 AMR exome

AF:

0.00348

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000290

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000104

Gnomad4 OTH exome

AF:

0.00460

GnomAD4 genome

AF:

0.0171

AC:

2572

AN:

150480

Hom.:

Cov.:

AF XY:

0.0166

AC XY:

1216

AN XY:

73406

show subpopulations

Gnomad4 AFR

AF:

0.0593

Gnomad4 AMR

AF:

0.00641

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000212

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000251

Gnomad4 OTH

AF:

0.0111

Alfa

AF:

0.00732

Hom.:

Bravo

AF:

0.0197

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 12, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

6.3

DANN

Benign

0.59

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over