8-11769752-C-G

Variant names:

• chr8-11769752-C-G
• rs8191518
• ENST00000284503:c.-586C>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145043.4(NEIL2):​c.-586C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,396 control chromosomes in the GnomAD database, including 2,294 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 0.15 (2285 hom., cov: 33)
  • Exomes 𝑓: 0.26 (9 hom.)
• Consequence: NEIL2 NM_145043.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.266

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]

LOC124901888 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEIL2	NM_145043.4	c.-586C>G		5_prime_UTR_variant	Exon 1 of 5	ENST00000284503.7	NP_659480.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEIL2	ENST00000284503	c.-586C>G		5_prime_UTR_variant	Exon 1 of 5	2	NM_145043.4	ENSP00000284503.6

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22977 AN: 152128 Hom.: 2292 Cov.: 33

Gnomad AFR AF: 0.0451

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.177

GnomAD4 exome AF: 0.257 AC: 39 AN: 152 Hom.: 9 Cov.: 0 AF XY: 0.275 AC XY: 33 AN XY: 120

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 SAS exome AF: 0.333

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.261

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.151 AC: 22963 AN: 152244 Hom.: 2285 Cov.: 33 AF XY: 0.143 AC XY: 10647 AN XY: 74450

Gnomad4 AFR AF: 0.0450

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.229

Gnomad4 EAS AF: 0.00194

Gnomad4 SAS AF: 0.177

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.228

Gnomad4 OTH AF: 0.175

Alfa AF: 0.0914 Hom.: 135

Bravo AF: 0.146

Asia WGS AF: 0.0630 AC: 222 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	12
DANN	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs8191518; hg19: chr8-11627261;