rs804292

Variant names:

• chr8-11786406-G-A
• rs804292
• NM_145043.4:c.*133G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-11786406-G-A
• chr8-11786406-G-C
• chr8-11786406-G-T

Variant summary

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

The NM_145043.4(NEIL2):​c.*133G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.78 in 848,968 control chromosomes in the GnomAD database, including 259,984 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 0.78 (46290 hom., cov: 31)
  • Exomes 𝑓: 0.78 (213694 hom.)
• Consequence: NEIL2 NM_145043.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.688
• Publications: 23 publications found

Genes affected

NEIL2 (HGNC:18956): (nei like DNA glycosylase 2) This gene encodes a member of the Fpg/Nei family of DNA glycosylases. These glycosylases initiate the first step in base excision repair by cleaving oxidatively damaged bases and introducing a DNA strand break via their abasic site lyase activity. This enzyme is primarily associated with DNA repair during transcription and acts prefentially on cytosine-derived lesions, particularly 5-hydroxyuracil and 5-hydroxycytosine. It contains an N-terminal catalytic domain, a hinge region, and a C-terminal DNA-binding domain with helix-two-turn-helix and zinc finger motifs. This enzyme interacts with the X-ray cross complementing factor 1 scaffold protein as part of a multi-protein DNA repair complex. A pseudogene of this gene has been identified. [provided by RefSeq, Mar 2017]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145043.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEIL2	NM_145043.4	MANE Select	c.*133G>A		3_prime_UTR	Exon 5 of 5	NP_659480.1
	NEIL2	NR_146180.2		n.1788G>A		non_coding_transcript_exon	Exon 5 of 5
	NEIL2	NR_146181.2		n.1955G>A		non_coding_transcript_exon	Exon 6 of 6

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEIL2	ENST00000284503.7	TSL:2 MANE Select	c.*133G>A		3_prime_UTR	Exon 5 of 5	ENSP00000284503.6
	NEIL2	ENST00000436750.7	TSL:1	c.*133G>A		3_prime_UTR	Exon 5 of 5	ENSP00000394023.2
	NEIL2	ENST00000524741.1	TSL:2	n.1232G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.779 AC: 118306 AN: 151944 Hom.: 46242 Cov.: 31

Gnomad AFR AF: 0.753

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.839

Gnomad ASJ AF: 0.760

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.809

Gnomad FIN AF: 0.843

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.755

Gnomad OTH AF: 0.775

GnomAD4 exome AF: 0.780 AC: 543547 AN: 696906 Hom.: 213694 Cov.: 9 AF XY: 0.780 AC XY: 285957 AN XY: 366480

African (AFR) AF: 0.755 AC: 13714 AN: 18174

American (AMR) AF: 0.876 AC: 29987 AN: 34224

Ashkenazi Jewish (ASJ) AF: 0.763 AC: 15602 AN: 20454

East Asian (EAS) AF: 0.999 AC: 32476 AN: 32514

South Asian (SAS) AF: 0.803 AC: 51449 AN: 64080

European-Finnish (FIN) AF: 0.837 AC: 38115 AN: 45550

Middle Eastern (MID) AF: 0.762 AC: 2040 AN: 2678

European-Non Finnish (NFE) AF: 0.749 AC: 333104 AN: 444548

Other (OTH) AF: 0.780 AC: 27060 AN: 34684

GnomAD4 genome AF: 0.779 AC: 118415 AN: 152062 Hom.: 46290 Cov.: 31 AF XY: 0.788 AC XY: 58601 AN XY: 74330

African (AFR) AF: 0.753 AC: 31231 AN: 41448

American (AMR) AF: 0.840 AC: 12822 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.760 AC: 2636 AN: 3470

East Asian (EAS) AF: 0.996 AC: 5152 AN: 5172

South Asian (SAS) AF: 0.809 AC: 3900 AN: 4818

European-Finnish (FIN) AF: 0.843 AC: 8926 AN: 10586

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.755 AC: 51299 AN: 67978

Other (OTH) AF: 0.777 AC: 1641 AN: 2112

Alfa AF: 0.767 Hom.: 146784

Bravo AF: 0.777

Asia WGS AF: 0.918 AC: 3189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.14
DANN	Benign	0.52
PhyloP100		-0.69
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: rs804292; hg19: chr8-11643915;