chr4-177321244-G-A

Variant names:

• chr4-177321244-G-A
• rs6830266
• NM_018248.3:c.157-1215G>A

Variant summary

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

The NM_018248.3(NEIL3):​c.157-1215G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 151,896 control chromosomes in the GnomAD database, including 7,355 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 0.27 (7355 hom., cov: 32)
• Consequence: NEIL3 NM_018248.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.221
• Publications: 9 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEIL3	NM_018248.3	c.157-1215G>A		intron_variant	Intron 1 of 9	ENST00000264596.4	NP_060718.3
NEIL3	XM_047415894.1	c.157-1215G>A		intron_variant	Intron 1 of 11		XP_047271850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEIL3	ENST00000264596.4	c.157-1215G>A		intron_variant	Intron 1 of 9	1	NM_018248.3	ENSP00000264596.3
NEIL3	ENST00000513321.1	n.156+11135G>A		intron_variant	Intron 1 of 3	1		ENSP00000424735.1

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40842 AN: 151780 Hom.: 7330 Cov.: 32

Gnomad AFR AF: 0.504

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.0867

Gnomad MID AF: 0.290

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.269 AC: 40914 AN: 151896 Hom.: 7355 Cov.: 32 AF XY: 0.265 AC XY: 19671 AN XY: 74264

African (AFR) AF: 0.505 AC: 20890 AN: 41384

American (AMR) AF: 0.266 AC: 4059 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 716 AN: 3472

East Asian (EAS) AF: 0.280 AC: 1448 AN: 5168

South Asian (SAS) AF: 0.184 AC: 888 AN: 4814

European-Finnish (FIN) AF: 0.0867 AC: 914 AN: 10540

Middle Eastern (MID) AF: 0.295 AC: 86 AN: 292

European-Non Finnish (NFE) AF: 0.165 AC: 11199 AN: 67958

Other (OTH) AF: 0.277 AC: 582 AN: 2102

Alfa AF: 0.189 Hom.: 4850

Bravo AF: 0.296

Asia WGS AF: 0.256 AC: 889 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.1
DANN	Benign	0.68
PhyloP100		0.22
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: rs6830266; hg19: chr4-178242398; COSMIC: COSV52810855;