Variant 2-219076341-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.*40C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 1,613,646 control chromosomes in the GnomAD database, including 450,717 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.72 ( 40298 hom., cov: 30)

Exomes 𝑓: 0.75 ( 410419 hom. )

Consequence

NHEJ1
NM_024782.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.25

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:

ENSG00000280537 (HGNC:):

ENSG00000280537 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=-0.81).

BP6

Variant 2-219076341-G-A is Benign according to our data. Variant chr2-219076341-G-A is described in ClinVar as [Benign]. Clinvar id is 1268786.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-219076341-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
NHEJ1	NM_024782.3 link	c.*40C>T	3_prime_UTR_variant	Exon 8 of 8	ENST00000356853.10	NP_079058.1	Q9H9Q4-1
NHEJ1	NM_001377499.1 link	c.*40C>T	3_prime_UTR_variant	Exon 8 of 8		NP_001364428.1
NHEJ1	NM_001377498.1 link	c.*40C>T	3_prime_UTR_variant	Exon 8 of 8		NP_001364427.1
NHEJ1	NR_165304.1 link	n.1118C>T	non_coding_transcript_exon_variant	Exon 9 of 9

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
NHEJ1	ENST00000356853 link	c.*40C>T	3_prime_UTR_variant	Exon 8 of 8	1	NM_024782.3	ENSP00000349313.5	Q9H9Q4-1
ENSG00000280537	ENST00000318673.6 link	n.*2062C>T	non_coding_transcript_exon_variant	Exon 17 of 17	2		ENSP00000320919.3	F8W735
ENSG00000280537	ENST00000318673.6 link	n.*2062C>T	3_prime_UTR_variant	Exon 17 of 17	2		ENSP00000320919.3	F8W735

Frequencies

GnomAD3 genomes

AF:

0.724

AC:

109958

AN:

151806

Hom.:

40287

Cov.:

show subpopulations

Gnomad AFR

AF:

0.704

Gnomad AMI

AF:

0.652

Gnomad AMR

AF:

0.646

Gnomad ASJ

AF:

0.727

Gnomad EAS

AF:

0.446

Gnomad SAS

AF:

0.636

Gnomad FIN

AF:

0.820

Gnomad MID

AF:

0.661

Gnomad NFE

AF:

0.769

Gnomad OTH

AF:

0.700

GnomAD3 exomes

AF:

0.707

AC:

177663

AN:

251122

Hom.:

64107

AF XY:

0.710

AC XY:

96444

AN XY:

135760

show subpopulations

Gnomad AFR exome

AF:

0.704

Gnomad AMR exome

AF:

0.619

Gnomad ASJ exome

AF:

0.728

Gnomad EAS exome

AF:

0.456

Gnomad SAS exome

AF:

0.646

Gnomad FIN exome

AF:

0.824

Gnomad NFE exome

AF:

0.769

Gnomad OTH exome

AF:

0.697

GnomAD4 exome

AF:

0.746

AC:

1090581

AN:

1461720

Hom.:

410419

Cov.:

AF XY:

0.744

AC XY:

540898

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.699

Gnomad4 AMR exome

AF:

0.620

Gnomad4 ASJ exome

AF:

0.730

Gnomad4 EAS exome

AF:

0.456

Gnomad4 SAS exome

AF:

0.652

Gnomad4 FIN exome

AF:

0.821

Gnomad4 NFE exome

AF:

0.769

Gnomad4 OTH exome

AF:

0.721

GnomAD4 genome

AF:

0.724

AC:

110011

AN:

151926

Hom.:

40298

Cov.:

AF XY:

0.722

AC XY:

53572

AN XY:

74246

show subpopulations

Gnomad4 AFR

AF:

0.703

Gnomad4 AMR

AF:

0.646

Gnomad4 ASJ

AF:

0.727

Gnomad4 EAS

AF:

0.446

Gnomad4 SAS

AF:

0.636

Gnomad4 FIN

AF:

0.820

Gnomad4 NFE

AF:

0.769

Gnomad4 OTH

AF:

0.696

Alfa

AF:

0.750

Hom.:

85130

Bravo

AF:

0.708

Asia WGS

AF:

0.495

AC:

1725

AN:

3478

EpiCase

AF:

0.754

EpiControl

AF:

0.756

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 86% of patients studied by a panel of primary immunodeficiencies. Number of patients: 83. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.4

DANN

Benign

0.74

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