8-11778437-T-C

Variant names:

• chr8-11778437-T-C
• rs4840583
• NM_145043.4:c.139-1161T>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.139-1161T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 151,874 control chromosomes in the GnomAD database, including 16,961 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 0.46 (16961 hom., cov: 30)
• Consequence: NEIL2 NM_145043.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.164
• Publications: 14 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.542 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEIL2	NM_145043.4	MANE Select	c.139-1161T>C		intron	N/A	NP_659480.1	Q969S2-1
	NEIL2	NM_001135746.3		c.139-1161T>C		intron	N/A	NP_001129218.1	Q969S2-1
	NEIL2	NM_001349442.2		c.139-1161T>C		intron	N/A	NP_001336371.1	Q969S2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEIL2	ENST00000284503.7	TSL:2 MANE Select	c.139-1161T>C		intron	N/A	ENSP00000284503.6	Q969S2-1
	NEIL2	ENST00000436750.7	TSL:1	c.139-1161T>C		intron	N/A	ENSP00000394023.2	Q969S2-1
	NEIL2	ENST00000455213.6	TSL:5	c.139-1161T>C		intron	N/A	ENSP00000397538.2	Q969S2-1

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69325 AN: 151756 Hom.: 16969 Cov.: 30

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.482

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

GnomAD4 genome AF: 0.457 AC: 69331 AN: 151874 Hom.: 16961 Cov.: 30 AF XY: 0.457 AC XY: 33888 AN XY: 74222

African (AFR) AF: 0.266 AC: 11008 AN: 41422

American (AMR) AF: 0.489 AC: 7462 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.548 AC: 1896 AN: 3460

East Asian (EAS) AF: 0.460 AC: 2368 AN: 5144

South Asian (SAS) AF: 0.477 AC: 2292 AN: 4804

European-Finnish (FIN) AF: 0.517 AC: 5450 AN: 10544

Middle Eastern (MID) AF: 0.466 AC: 136 AN: 292

European-Non Finnish (NFE) AF: 0.547 AC: 37166 AN: 67932

Other (OTH) AF: 0.482 AC: 1017 AN: 2112

Alfa AF: 0.516 Hom.: 78976

Bravo AF: 0.448

Asia WGS AF: 0.444 AC: 1544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.8
DANN	Benign	0.34
PhyloP100		-0.16
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: rs4840583; hg19: chr8-11635946;