chr8-11778060-T-C

Variant names:

• chr8-11778060-T-C
• rs4840581
• NM_145043.4:c.139-1538T>C

Variant summary

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

The NM_145043.4(NEIL2):​c.139-1538T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 152,088 control chromosomes in the GnomAD database, including 20,123 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 0.50 (20123 hom., cov: 33)
• Consequence: NEIL2 NM_145043.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0230
• Publications: 8 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 (AFR) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEIL2	NM_145043.4	c.139-1538T>C		intron_variant	Intron 2 of 4	ENST00000284503.7	NP_659480.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEIL2	ENST00000284503.7	c.139-1538T>C		intron_variant	Intron 2 of 4	2	NM_145043.4	ENSP00000284503.6

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75840 AN: 151970 Hom.: 20122 Cov.: 33

Gnomad AFR AF: 0.554

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.664

Gnomad EAS AF: 0.0202

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.549

Gnomad OTH AF: 0.533

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

GnomAD4 genome AF: 0.499 AC: 75866 AN: 152088 Hom.: 20123 Cov.: 33 AF XY: 0.482 AC XY: 35822 AN XY: 74364

African (AFR) AF: 0.554 AC: 22966 AN: 41462

American (AMR) AF: 0.382 AC: 5835 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.664 AC: 2307 AN: 3472

East Asian (EAS) AF: 0.0203 AC: 105 AN: 5182

South Asian (SAS) AF: 0.406 AC: 1961 AN: 4830

European-Finnish (FIN) AF: 0.344 AC: 3635 AN: 10576

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.549 AC: 37329 AN: 67964

Other (OTH) AF: 0.526 AC: 1111 AN: 2112

Alfa AF: 0.506 Hom.: 10507

Bravo AF: 0.501

Asia WGS AF: 0.223 AC: 782 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.8
DANN	Benign	0.73
PhyloP100		0.023
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: rs4840581; hg19: chr8-11635569;