rs987467

Variant names:

• chr4-177324015-T-C
• rs987467
• NM_018248.3:c.278+1435T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018248.3(NEIL3):​c.278+1435T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 152,016 control chromosomes in the GnomAD database, including 26,457 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 0.58 (26457 hom., cov: 32)
• Consequence: NEIL3 NM_018248.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.473
• Publications: 4 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEIL3	NM_018248.3	c.278+1435T>C		intron_variant	Intron 2 of 9	ENST00000264596.4	NP_060718.3
NEIL3	XM_047415894.1	c.278+1435T>C		intron_variant	Intron 2 of 11		XP_047271850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEIL3	ENST00000264596.4	c.278+1435T>C		intron_variant	Intron 2 of 9	1	NM_018248.3	ENSP00000264596.3
NEIL3	ENST00000513321.1	n.157-11673T>C		intron_variant	Intron 1 of 3	1		ENSP00000424735.1

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88026 AN: 151898 Hom.: 26408 Cov.: 32

Gnomad AFR AF: 0.744

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.565

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

GnomAD4 genome AF: 0.580 AC: 88134 AN: 152016 Hom.: 26457 Cov.: 32 AF XY: 0.571 AC XY: 42401 AN XY: 74312

African (AFR) AF: 0.744 AC: 30855 AN: 41460

American (AMR) AF: 0.505 AC: 7709 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 1815 AN: 3468

East Asian (EAS) AF: 0.451 AC: 2328 AN: 5164

South Asian (SAS) AF: 0.502 AC: 2419 AN: 4818

European-Finnish (FIN) AF: 0.442 AC: 4663 AN: 10560

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.539 AC: 36652 AN: 67962

Other (OTH) AF: 0.565 AC: 1191 AN: 2108

Alfa AF: 0.562 Hom.: 8938

Bravo AF: 0.592

Asia WGS AF: 0.518 AC: 1803 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.26
DANN	Benign	0.53
PhyloP100		-0.47
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: rs987467; hg19: chr4-178245169;