Variant 4-177339718-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000264596.4(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
ENST00000264596.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.697

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 made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
NEIL3	NM_018248.3 linkuse as main transcript	c.628-65C>T		intron_variant		ENST00000264596.4	NP_060718.3
NEIL3	XM_047415894.1 linkuse as main transcript	c.628-65C>T		intron_variant			XP_047271850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEIL3	ENST00000264596.4 linkuse as main transcript	c.628-65C>T		intron_variant		1	NM_018248.3	ENSP00000264596	P1
NEIL3	ENST00000513321.1 linkuse as main transcript	c.*313+3397C>T		intron_variant, NMD_transcript_variant		1		ENSP00000424735

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

Gnomad4 AFR exome

AF:

0.0327

Gnomad4 AMR exome

AF:

0.147

Gnomad4 ASJ exome

AF:

0.0666

Gnomad4 EAS exome

AF:

0.319

Gnomad4 SAS exome

AF:

0.154

Gnomad4 FIN exome

AF:

0.129

Gnomad4 NFE exome

AF:

0.128

Gnomad4 OTH exome

AF:

0.126

GnomAD4 genome

AF:

0.104

AC:

15828

AN:

152112

Hom.:

1036

Cov.:

AF XY:

0.105

AC XY:

7842

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.0374

Gnomad4 AMR

AF:

0.112

Gnomad4 ASJ

AF:

0.0608

Gnomad4 EAS

AF:

0.302

Gnomad4 SAS

AF:

0.164

Gnomad4 FIN

AF:

0.136

Gnomad4 NFE

AF:

0.122

Gnomad4 OTH

AF:

0.0920

Alfa

AF:

0.111

Hom.:

1358

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

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

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

DANN

Benign

0.71

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

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