Genetic Variant NEIL3:c.628-65C>T (chr4-177339718-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_018248.3(NEIL3):c.628-65C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 1,016,098 control chromosomes in the GnomAD database, including 9,914 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.10 ( 1036 hom., cov: 32)

Exomes 𝑓: 0.13 ( 8878 hom. )

Consequence

NEIL3
NM_018248.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.697

Publications

15 publications found

Variant links:

Genes affected

NEIL3 (HGNC:24573): (nei like DNA glycosylase 3) NEIL3 belongs to a class of DNA glycosylases homologous to the bacterial Fpg/Nei family. These glycosylases initiate the first step in base excision repair by cleaving bases damaged by reactive oxygen species and introducing a DNA strand break via the associated lyase reaction (Bandaru et al., 2002 [PubMed 12509226]).[supplied by OMIM, Mar 2008]

NEIL3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 4-177339718-C-T is Benign according to our data. Variant chr4-177339718-C-T is described in ClinVar as Benign. ClinVar VariationId is 2688480.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEIL3	NM_018248.3 link	c.628-65C>T		intron_variant	Intron 4 of 9	ENST00000264596.4	NP_060718.3	Q8TAT5
NEIL3	XM_047415894.1 link	c.628-65C>T		intron_variant	Intron 4 of 11		XP_047271850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEIL3	ENST00000264596.4 link	c.628-65C>T		intron_variant	Intron 4 of 9	1	NM_018248.3	ENSP00000264596.3		Q8TAT5
NEIL3	ENST00000513321.1 link	n.*313+3397C>T		intron_variant	Intron 3 of 3	1		ENSP00000424735.1		D6RAV1

Frequencies

GnomAD3 genomes

AF:

0.104

AC:

15821

AN:

151994

Hom.:

1036

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0373

Gnomad AMI

AF:

0.0625

Gnomad AMR

AF:

0.112

Gnomad ASJ

AF:

0.0608

Gnomad EAS

AF:

0.302

Gnomad SAS

AF:

0.164

Gnomad FIN

AF:

0.136

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.122

Gnomad OTH

AF:

0.0920

GnomAD4 exome

AF:

0.135

AC:

116541

AN:

863986

Hom.:

8878

AF XY:

0.135

AC XY:

60903

AN XY:

452252

show subpopulations

African (AFR)

AF:

0.0327

AC:

692

AN:

21144

American (AMR)

AF:

0.147

AC:

5652

AN:

38492

Ashkenazi Jewish (ASJ)

AF:

0.0666

AC:

1423

AN:

21362

East Asian (EAS)

AF:

0.319

AC:

11635

AN:

36478

South Asian (SAS)

AF:

0.154

AC:

10812

AN:

69990

European-Finnish (FIN)

AF:

0.129

AC:

6599

AN:

51162

Middle Eastern (MID)

AF:

0.0632

AC:

286

AN:

4526

European-Non Finnish (NFE)

AF:

0.128

AC:

74378

AN:

580498

Other (OTH)

AF:

0.126

AC:

5064

AN:

40334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

4825

9650

14475

19300

24125

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2034

4068

6102

8136

10170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.104

AC:

15828

AN:

152112

Hom.:

1036

Cov.:

AF XY:

0.105

AC XY:

7842

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.0374

AC:

1551

AN:

41510

American (AMR)

AF:

0.112

AC:

1714

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.0608

AC:

211

AN:

3470

East Asian (EAS)

AF:

0.302

AC:

1562

AN:

5174

South Asian (SAS)

AF:

0.164

AC:

791

AN:

4814

European-Finnish (FIN)

AF:

0.136

AC:

1433

AN:

10558

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.122

AC:

8297

AN:

68008

Other (OTH)

AF:

0.0920

AC:

194

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

715

1429

2144

2858

3573

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

376

564

752

940

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.111

Hom.:

1693

Bravo

AF:

0.103

Asia WGS

AF:

0.222

AC:

772

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jan 24, 2024

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 25% of patients studied by a panel of primary immunodeficiencies. Number of patients: 22. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.2

(source)

DANN

Benign

0.71

PhyloP100

-0.70

Mutation Taster

=19/81

disease causing (long InDel)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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.

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