Variant chr2-219077217-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_024782.3(NHEJ1):c.825+29G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0177 in 1,549,942 control chromosomes in the GnomAD database, including 281 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 22 hom., cov: 32)

Exomes 𝑓: 0.018 ( 259 hom. )

Consequence

NHEJ1
NM_024782.3 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.54

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=-0.85).

BP6

Variant 2-219077217-C-T is Benign according to our data. Variant chr2-219077217-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1200626.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-219077217-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0142 (2168/152312) while in subpopulation NFE AF= 0.022 (1495/68028). AF 95% confidence interval is 0.021. There are 22 homozygotes in gnomad4. There are 1042 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
NHEJ1	NM_024782.3 linkuse as main transcript	c.825+29G>A	intron_variant	ENST00000356853.10	NP_079058.1
NHEJ1	NM_001377498.1 linkuse as main transcript	c.825+29G>A	intron_variant		NP_001364427.1
NHEJ1	NM_001377499.1 linkuse as main transcript	c.840+29G>A	intron_variant		NP_001364428.1
NHEJ1	NR_165304.1 linkuse as main transcript	n.1003+29G>A	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.825+29G>A		intron_variant		1	NM_024782.3	ENSP00000349313	P4	Q9H9Q4-1

Frequencies

GnomAD3 genomes

AF:

0.0143

AC:

2169

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00263

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.0105

Gnomad ASJ

AF:

0.00950

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00683

Gnomad FIN

AF:

0.0281

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0220

Gnomad OTH

AF:

0.0124

GnomAD3 exomes

AF:

0.0153

AC:

3847

AN:

251018

Hom.:

AF XY:

0.0154

AC XY:

2091

AN XY:

135676

show subpopulations

Gnomad AFR exome

AF:

0.00246

Gnomad AMR exome

AF:

0.00790

Gnomad ASJ exome

AF:

0.00923

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00657

Gnomad FIN exome

AF:

0.0292

Gnomad NFE exome

AF:

0.0221

Gnomad OTH exome

AF:

0.0158

GnomAD4 exome

AF:

0.0181

AC:

25333

AN:

1397630

Hom.:

259

Cov.:

AF XY:

0.0177

AC XY:

12358

AN XY:

699372

show subpopulations

Gnomad4 AFR exome

AF:

0.00256

Gnomad4 AMR exome

AF:

0.00784

Gnomad4 ASJ exome

AF:

0.0102

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00602

Gnomad4 FIN exome

AF:

0.0286

Gnomad4 NFE exome

AF:

0.0205

Gnomad4 OTH exome

AF:

0.0157

GnomAD4 genome

AF:

0.0142

AC:

2168

AN:

152312

Hom.:

Cov.:

AF XY:

0.0140

AC XY:

1042

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00262

Gnomad4 AMR

AF:

0.0105

Gnomad4 ASJ

AF:

0.00950

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00684

Gnomad4 FIN

AF:

0.0281

Gnomad4 NFE

AF:

0.0220

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.0196

Hom.:

Bravo

AF:

0.0119

Asia WGS

AF:

0.00520

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 05, 2018	- -
Likely 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

-0.85

CADD

Benign

0.18

DANN

Benign

0.71

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