rs987467

Positions:

• chr4-177324015-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
NEIL3	NM_018248.3	c.278+1435T>C		intron_variant		ENST00000264596.4	NP_060718.3
NEIL3	XM_047415894.1	c.278+1435T>C		intron_variant			XP_047271850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEIL3	ENST00000264596.4	c.278+1435T>C		intron_variant		1	NM_018248.3	ENSP00000264596.3
NEIL3	ENST00000513321.1	n.157-11673T>C		intron_variant		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

Gnomad4 AFR AF: 0.744

Gnomad4 AMR AF: 0.505

Gnomad4 ASJ AF: 0.523

Gnomad4 EAS AF: 0.451

Gnomad4 SAS AF: 0.502

Gnomad4 FIN AF: 0.442

Gnomad4 NFE AF: 0.539

Gnomad4 OTH AF: 0.565

Alfa AF: 0.559 Hom.: 5410

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

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: rs987467; hg19: chr4-178245169;