rs1874546

Positions:

• chr8-11781369-C-G
• chr8-11781369-C-T

Variant summary

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

The NM_145043.4(NEIL2):​c.491+1419C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,122 control chromosomes in the GnomAD database, including 4,024 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 0.22 (4024 hom., cov: 32)
• Consequence: NEIL2 NM_145043.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.523

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEIL2	NM_145043.4	c.491+1419C>G		intron_variant		ENST00000284503.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEIL2	ENST00000284503.7	c.491+1419C>G		intron_variant		2	NM_145043.4	P1

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32947 AN: 152004 Hom.: 4021 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.223

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

GnomAD4 genome AF: 0.217 AC: 32975 AN: 152122 Hom.: 4024 Cov.: 32 AF XY: 0.224 AC XY: 16639 AN XY: 74348

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.180

Gnomad4 EAS AF: 0.469

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.255

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.225

Alfa AF: 0.204 Hom.: 419

Bravo AF: 0.220

Asia WGS AF: 0.339 AC: 1174 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.55
DANN	Benign	0.61

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: rs1874546; hg19: chr8-11638878;