rs73991015

Variant names:

• chr2-219076555-G-A
• rs73991015
• NM_024782.3:c.826-100C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-219076555-G-A
• chr2-219076555-G-C
• chr2-219076555-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024782.3(NHEJ1):​c.826-100C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00477 in 756,028 control chromosomes in the GnomAD database, including 110 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (74 hom., cov: 30)
  • Exomes 𝑓: 0.0020 (36 hom.)
• Consequence: NHEJ1 NM_024782.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0920
• Publications: 0 publications found

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)

ENSG00000280537 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 2-219076555-G-A is Benign according to our data. Variant chr2-219076555-G-A is described in ClinVar as [Benign]. Clinvar id is 1261938.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NHEJ1	NM_024782.3	c.826-100C>T		intron_variant	Intron 7 of 7	ENST00000356853.10	NP_079058.1
NHEJ1	NM_001377499.1	c.841-100C>T		intron_variant	Intron 7 of 7		NP_001364428.1
NHEJ1	NM_001377498.1	c.826-100C>T		intron_variant	Intron 7 of 7		NP_001364427.1
NHEJ1	NR_165304.1	n.1004-100C>T		intron_variant	Intron 8 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NHEJ1	ENST00000356853.10	c.826-100C>T		intron_variant	Intron 7 of 7	1	NM_024782.3	ENSP00000349313.5
ENSG00000280537	ENST00000318673.6	n.*1948-100C>T		intron_variant	Intron 16 of 16	2		ENSP00000320919.3

Frequencies

GnomAD3 genomes AF: 0.0163 AC: 2407 AN: 147686 Hom.: 74 Cov.: 30

Gnomad AFR AF: 0.0570

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00660

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000213

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000149

Gnomad OTH AF: 0.0123

GnomAD4 exome AF: 0.00198 AC: 1203 AN: 608314 Hom.: 36 AF XY: 0.00165 AC XY: 528 AN XY: 320950

African (AFR) AF: 0.0616 AC: 896 AN: 14536

American (AMR) AF: 0.00542 AC: 117 AN: 21572

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16428

East Asian (EAS) AF: 0.00 AC: 0 AN: 30134

South Asian (SAS) AF: 0.000111 AC: 6 AN: 53814

European-Finnish (FIN) AF: 0.0000344 AC: 1 AN: 29098

Middle Eastern (MID) AF: 0.00125 AC: 3 AN: 2396

European-Non Finnish (NFE) AF: 0.000132 AC: 54 AN: 409728

Other (OTH) AF: 0.00412 AC: 126 AN: 30608

GnomAD4 genome AF: 0.0163 AC: 2406 AN: 147714 Hom.: 74 Cov.: 30 AF XY: 0.0155 AC XY: 1117 AN XY: 71842

African (AFR) AF: 0.0569 AC: 2272 AN: 39934

American (AMR) AF: 0.00659 AC: 98 AN: 14862

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3448

East Asian (EAS) AF: 0.00 AC: 0 AN: 5080

South Asian (SAS) AF: 0.000214 AC: 1 AN: 4676

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9286

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.000149 AC: 10 AN: 67192

Other (OTH) AF: 0.0122 AC: 25 AN: 2044

Alfa AF: 0.000497 Hom.: 0

Bravo AF: 0.0181

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.61
DANN	Benign	0.61
PhyloP100		-0.092
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs73991015; hg19: chr2-219941277;