chr4-177351876-A-G

Variant names:

• chr4-177351876-A-G
• rs3828488
• NM_018248.3:c.1039+327A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_018248.3(NEIL3):​c.1039+327A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,058 control chromosomes in the GnomAD database, including 3,730 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.20 (3730 hom., cov: 33)
• Consequence: NEIL3 NM_018248.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.74
• Publications: 6 publications found

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]

ENSG00000249084 (HGNC:58914):

LOC105377558 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018248.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEIL3	NM_018248.3	MANE Select	c.1039+327A>G		intron	N/A	NP_060718.3	Q8TAT5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEIL3	ENST00000264596.4	TSL:1 MANE Select	c.1039+327A>G		intron	N/A	ENSP00000264596.3	Q8TAT5
	NEIL3	ENST00000513321.1	TSL:1	n.*314-1432A>G		intron	N/A	ENSP00000424735.1	D6RAV1
	NEIL3	ENST00000905043.1		c.922+327A>G		intron	N/A	ENSP00000575102.1

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29674 AN: 151940 Hom.: 3703 Cov.: 33

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.0893

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.168

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.196 AC: 29747 AN: 152058 Hom.: 3730 Cov.: 33 AF XY: 0.200 AC XY: 14845 AN XY: 74312

African (AFR) AF: 0.317 AC: 13140 AN: 41452

American (AMR) AF: 0.324 AC: 4944 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0893 AC: 310 AN: 3472

East Asian (EAS) AF: 0.250 AC: 1289 AN: 5156

South Asian (SAS) AF: 0.206 AC: 996 AN: 4828

European-Finnish (FIN) AF: 0.141 AC: 1492 AN: 10568

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7117 AN: 67994

Other (OTH) AF: 0.166 AC: 350 AN: 2110

Alfa AF: 0.140 Hom.: 2811

Bravo AF: 0.211

Asia WGS AF: 0.232 AC: 805 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	17
DANN	Benign	0.82
PhyloP100		1.7
Mutation Taster		=100/0	polymorphism (auto)

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: rs3828488; hg19: chr4-178273030;