rs8191649

Variant names:

• chr8-11783898-C-T
• rs8191649
• NM_145043.4:c.688+499C>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.688+499C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,154 control chromosomes in the GnomAD database, including 2,777 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 0.18 (2777 hom., cov: 33)
• Consequence: NEIL2 NM_145043.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.79
• Publications: 9 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEIL2	NM_145043.4	c.688+499C>T		intron_variant	Intron 4 of 4	ENST00000284503.7	NP_659480.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEIL2	ENST00000284503.7	c.688+499C>T		intron_variant	Intron 4 of 4	2	NM_145043.4	ENSP00000284503.6

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27791 AN: 152036 Hom.: 2774 Cov.: 33

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.0154

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.183 AC: 27790 AN: 152154 Hom.: 2777 Cov.: 33 AF XY: 0.177 AC XY: 13194 AN XY: 74378

African (AFR) AF: 0.159 AC: 6579 AN: 41502

American (AMR) AF: 0.158 AC: 2417 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1013 AN: 3470

East Asian (EAS) AF: 0.0155 AC: 80 AN: 5178

South Asian (SAS) AF: 0.165 AC: 795 AN: 4826

European-Finnish (FIN) AF: 0.134 AC: 1421 AN: 10592

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14740 AN: 67978

Other (OTH) AF: 0.205 AC: 433 AN: 2116

Alfa AF: 0.213 Hom.: 1862

Bravo AF: 0.181

Asia WGS AF: 0.104 AC: 360 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.16
DANN	Benign	0.49
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs8191649; hg19: chr8-11641407;