rs3828488

Positions:

• chr4-177351876-A-G
• chr4-177351876-A-T

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEIL3	NM_018248.3	c.1039+327A>G		intron_variant		ENST00000264596.4	NP_060718.3
LOC105377558	XR_007058384.1	n.216+5119T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEIL3	ENST00000264596.4	c.1039+327A>G		intron_variant		1	NM_018248.3	ENSP00000264596	P1
NEIL3	ENST00000513321.1	c.*314-1432A>G		intron_variant, NMD_transcript_variant		1		ENSP00000424735
	ENST00000506895.1	n.38+5119T>C		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.317

Gnomad4 AMR AF: 0.324

Gnomad4 ASJ AF: 0.0893

Gnomad4 EAS AF: 0.250

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.166

Alfa AF: 0.130 Hom.: 1917

Bravo AF: 0.211

Asia WGS AF: 0.232 AC: 805 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	17
DANN	Benign	0.82

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

Other links and lift over

dbSNP: rs3828488; hg19: chr4-178273030;