8-11770620-A-C

Position:

• chr8-11770620-A-C

Variant summary

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

The NM_145043.4(NEIL2):​c.-3+285A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,182 control chromosomes in the GnomAD database, including 2,783 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 0.18 (2783 hom., cov: 32)
• Consequence: NEIL2 NM_145043.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.573

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEIL2	NM_145043.4	c.-3+285A>C		intron_variant		ENST00000284503.7
LOC124901888	XR_007060824.1	n.574-212T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEIL2	ENST00000284503.7	c.-3+285A>C		intron_variant		2	NM_145043.4	P1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27088 AN: 152064 Hom.: 2783 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.0163

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.178 AC: 27084 AN: 152182 Hom.: 2783 Cov.: 32 AF XY: 0.173 AC XY: 12881 AN XY: 74406

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.295

Gnomad4 EAS AF: 0.0164

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.238

Gnomad4 OTH AF: 0.203

Alfa AF: 0.211 Hom.: 566

Bravo AF: 0.172

Asia WGS AF: 0.109 AC: 380 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.5
DANN	Benign	0.33

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: rs904009; hg19: chr8-11628129;