Genetic Variant NM_024782.3:c.826-112_826-103delAAAAAAAAAA (chr2-219076557-CTTTTTTTTTT-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_024782.3(NHEJ1):c.826-112_826-103delAAAAAAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0073 in 457,698 control chromosomes in the GnomAD database, including 87 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.020 ( 79 hom., cov: 28)

Exomes 𝑓: 0.0028 ( 8 hom. )

Consequence

NHEJ1
NM_024782.3 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.16

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

Cernunnos-XLF deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)

NHEJ1 links:

ENSG00000280537 (HGNC:):

ENSG00000280537 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 2-219076557-CTTTTTTTTTT-C is Benign according to our data. Variant chr2-219076557-CTTTTTTTTTT-C is described in ClinVar as [Benign]. Clinvar id is 1225248.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
NHEJ1	NM_024782.3 link	c.826-112_826-103delAAAAAAAAAA	intron_variant	Intron 7 of 7	ENST00000356853.10	NP_079058.1	Q9H9Q4-1
NHEJ1	NM_001377499.1 link	c.841-112_841-103delAAAAAAAAAA	intron_variant	Intron 7 of 7		NP_001364428.1
NHEJ1	NM_001377498.1 link	c.826-112_826-103delAAAAAAAAAA	intron_variant	Intron 7 of 7		NP_001364427.1
NHEJ1	NR_165304.1 link	n.1004-112_1004-103delAAAAAAAAAA	intron_variant	Intron 8 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NHEJ1	ENST00000356853.10 link	c.826-112_826-103delAAAAAAAAAA		intron_variant	Intron 7 of 7	1	NM_024782.3	ENSP00000349313.5		Q9H9Q4-1
ENSG00000280537	ENST00000318673.6 link	n.1948-112_1948-103delAAAAAAAAAA		intron_variant	Intron 16 of 16	2		ENSP00000320919.3		F8W735

Frequencies

GnomAD3 genomes

AF:

0.0196

AC:

2398

AN:

122550

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0693

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00838

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000256

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000172

Gnomad OTH

AF:

0.0157

GnomAD4 exome

AF:

0.00282

AC:

946

AN:

335172

Hom.:

AF XY:

0.00224

AC XY:

413

AN XY:

183988

show subpopulations

African (AFR)

AF:

0.0793

AC:

709

AN:

8944

American (AMR)

AF:

0.00623

AC:

AN:

15420

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9718

East Asian (EAS)

AF:

0.00

AC:

AN:

18096

South Asian (SAS)

AF:

0.000116

AC:

AN:

43212

European-Finnish (FIN)

AF:

0.00

AC:

AN:

16876

Middle Eastern (MID)

AF:

0.00233

AC:

AN:

1290

European-Non Finnish (NFE)

AF:

0.000196

AC:

AN:

204184

Other (OTH)

AF:

0.00534

AC:

AN:

17432

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.522

Heterozygous variant carriers

120

150

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0196

AC:

2397

AN:

122526

Hom.:

Cov.:

AF XY:

0.0190

AC XY:

1116

AN XY:

58650

show subpopulations

African (AFR)

AF:

0.0692

AC:

2261

AN:

32660

American (AMR)

AF:

0.00838

AC:

AN:

11812

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2976

East Asian (EAS)

AF:

0.00

AC:

AN:

4400

South Asian (SAS)

AF:

0.000257

AC:

AN:

3884

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6128

Middle Eastern (MID)

AF:

0.00

AC:

AN:

230

European-Non Finnish (NFE)

AF:

0.000172

AC:

AN:

57984

Other (OTH)

AF:

0.0156

AC:

AN:

1662

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.579

Heterozygous variant carriers

174

260

347

434

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 13, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.2

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

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NM_024782.3:c.826-112_826-103delAAAAAAAAAA

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