rs2048077

Variant names:

• chr4-177334756-G-A
• rs2048077
• NM_018248.3:c.279-932G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-177334756-G-A
• chr4-177334756-G-T

Variant summary

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

The NM_018248.3(NEIL3):​c.279-932G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0374 in 152,206 control chromosomes in the GnomAD database, including 278 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 0.037 (278 hom., cov: 32)
• Consequence: NEIL3 NM_018248.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.883
• Publications: 5 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=-0.58).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEIL3	NM_018248.3	c.279-932G>A		intron_variant	Intron 2 of 9	ENST00000264596.4	NP_060718.3
NEIL3	XM_047415894.1	c.279-932G>A		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.279-932G>A		intron_variant	Intron 2 of 9	1	NM_018248.3	ENSP00000264596.3
NEIL3	ENST00000513321.1	n.157-932G>A		intron_variant	Intron 1 of 3	1		ENSP00000424735.1

Frequencies

GnomAD3 genomes AF: 0.0375 AC: 5696 AN: 152088 Hom.: 278 Cov.: 32

Gnomad AFR AF: 0.0113

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0720

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.0658

Gnomad FIN AF: 0.0174

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0302

Gnomad OTH AF: 0.0440

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

GnomAD4 genome AF: 0.0374 AC: 5698 AN: 152206 Hom.: 278 Cov.: 32 AF XY: 0.0383 AC XY: 2850 AN XY: 74408

African (AFR) AF: 0.0113 AC: 468 AN: 41538

American (AMR) AF: 0.0720 AC: 1101 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00749 AC: 26 AN: 3472

East Asian (EAS) AF: 0.278 AC: 1440 AN: 5178

South Asian (SAS) AF: 0.0656 AC: 316 AN: 4816

European-Finnish (FIN) AF: 0.0174 AC: 184 AN: 10586

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0302 AC: 2057 AN: 68002

Other (OTH) AF: 0.0459 AC: 97 AN: 2112

Alfa AF: 0.0247 Hom.: 30

Bravo AF: 0.0451

Asia WGS AF: 0.155 AC: 539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	7.4
DANN	Benign	0.63
PhyloP100		0.88
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: rs2048077; hg19: chr4-178255910;