rs8191663

Variant names:

• chr8-11785950-C-T
• rs8191663
• NM_145043.4:c.689-13C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-11785950-C-T
• chr8-11785950-C-G

Variant summary

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

The NM_145043.4(NEIL2):​c.689-13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 1,610,756 control chromosomes in the GnomAD database, including 44,963 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.25 (4936 hom., cov: 32)
  • Exomes 𝑓: 0.23 (40027 hom.)
• Consequence: NEIL2 NM_145043.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.562
• Publications: 16 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.313 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.689-13C>T		intron	N/A	NP_659480.1	Q969S2-1
	NEIL2	NM_001135746.3		c.689-13C>T		intron	N/A	NP_001129218.1	Q969S2-1
	NEIL2	NM_001349442.2		c.689-13C>T		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.689-13C>T		intron	N/A	ENSP00000284503.6	Q969S2-1
	NEIL2	ENST00000436750.7	TSL:1	c.689-13C>T		intron	N/A	ENSP00000394023.2	Q969S2-1
	NEIL2	ENST00000455213.6	TSL:5	c.689-13C>T		intron	N/A	ENSP00000397538.2	Q969S2-1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38105 AN: 151918 Hom.: 4930 Cov.: 32

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.245

GnomAD2 exomes AF: 0.228 AC: 56910 AN: 249942 AF XY: 0.227

Gnomad AFR exome AF: 0.325

Gnomad AMR exome AF: 0.158

Gnomad ASJ exome AF: 0.292

Gnomad EAS exome AF: 0.283

Gnomad FIN exome AF: 0.225

Gnomad NFE exome AF: 0.231

Gnomad OTH exome AF: 0.247

GnomAD4 exome AF: 0.231 AC: 337529 AN: 1458720 Hom.: 40027 Cov.: 33 AF XY: 0.231 AC XY: 167841 AN XY: 725768

African (AFR) AF: 0.329 AC: 10982 AN: 33400

American (AMR) AF: 0.165 AC: 7373 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 7523 AN: 26106

East Asian (EAS) AF: 0.265 AC: 10520 AN: 39682

South Asian (SAS) AF: 0.189 AC: 16307 AN: 86192

European-Finnish (FIN) AF: 0.227 AC: 12100 AN: 53378

Middle Eastern (MID) AF: 0.294 AC: 1690 AN: 5744

European-Non Finnish (NFE) AF: 0.231 AC: 256304 AN: 1109222

Other (OTH) AF: 0.244 AC: 14730 AN: 60278

GnomAD4 genome AF: 0.251 AC: 38129 AN: 152036 Hom.: 4936 Cov.: 32 AF XY: 0.248 AC XY: 18413 AN XY: 74318

African (AFR) AF: 0.318 AC: 13167 AN: 41436

American (AMR) AF: 0.194 AC: 2966 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1013 AN: 3466

East Asian (EAS) AF: 0.283 AC: 1467 AN: 5176

South Asian (SAS) AF: 0.176 AC: 848 AN: 4814

European-Finnish (FIN) AF: 0.211 AC: 2231 AN: 10566

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.230 AC: 15605 AN: 67990

Other (OTH) AF: 0.242 AC: 510 AN: 2104

Alfa AF: 0.245 Hom.: 2318

Bravo AF: 0.253

Asia WGS AF: 0.212 AC: 737 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.59
PhyloP100		-0.56
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: rs8191663; hg19: chr8-11643459; COSMIC: COSV52706860; COSMIC: COSV52706860;