2-219076341-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000318673.6(ENSG00000280537):n.*2062C>T variant causes a non coding transcript exon 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

ENSG00000280537
ENST00000318673.6 non_coding_transcript_exon

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.25

Publications

23 publications found

Variant links:

Genes affected

ENSG00000280537 (HGNC:):

ENSG00000280537 links:

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)

NHEJ1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

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	NR_165304.1 link	n.1118C>T	non_coding_transcript_exon_variant	Exon 9 of 9
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

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ENSG00000280537	ENST00000318673.6 link	n.*2062C>T	non_coding_transcript_exon_variant	Exon 17 of 17	2		ENSP00000320919.3	F8W735
NHEJ1	ENST00000356853.10 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	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

GnomAD2 exomes

AF:

0.707

AC:

177663

AN:

251122

AF XY:

0.710

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 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

African (AFR)

AF:

0.699

AC:

23391

AN:

33478

American (AMR)

AF:

0.620

AC:

27714

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.730

AC:

19068

AN:

26130

East Asian (EAS)

AF:

0.456

AC:

18088

AN:

39694

South Asian (SAS)

AF:

0.652

AC:

56242

AN:

86236

European-Finnish (FIN)

AF:

0.821

AC:

43874

AN:

53408

Middle Eastern (MID)

AF:

0.665

AC:

3818

AN:

5740

European-Non Finnish (NFE)

AF:

0.769

AC:

854828

AN:

1111938

Other (OTH)

AF:

0.721

AC:

43558

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

15724

31449

47173

62898

78622

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.724

AC:

110011

AN:

151926

Hom.:

40298

Cov.:

AF XY:

0.722

AC XY:

53572

AN XY:

74246

show subpopulations

African (AFR)

AF:

0.703

AC:

29094

AN:

41382

American (AMR)

AF:

0.646

AC:

9866

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.727

AC:

2521

AN:

3466

East Asian (EAS)

AF:

0.446

AC:

2298

AN:

5156

South Asian (SAS)

AF:

0.636

AC:

3069

AN:

4828

European-Finnish (FIN)

AF:

0.820

AC:

8666

AN:

10568

Middle Eastern (MID)

AF:

0.639

AC:

188

AN:

294

European-Non Finnish (NFE)

AF:

0.769

AC:

52246

AN:

67934

Other (OTH)

AF:

0.696

AC:

1471

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1519

3039

4558

6078

7597

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.745

Hom.:

131122

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

(source)

DANN

Benign

0.74

PhyloP100

-1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

2-219076341-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over