rs8191542

Positions:

• chr8-11772300-C-G
• chr8-11772300-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.138+715C>G 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 152,170 control chromosomes in the GnomAD database, including 2,641 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 (2641 hom., cov: 32)
• Consequence: NEIL2 NM_145043.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.197

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 (NFE) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEIL2	NM_145043.4	c.138+715C>G		intron_variant		ENST00000284503.7	NP_659480.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEIL2	ENST00000284503.7	c.138+715C>G		intron_variant		2	NM_145043.4	ENSP00000284503	P1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27089 AN: 152052 Hom.: 2648 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.00192

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.178 AC: 27080 AN: 152170 Hom.: 2641 Cov.: 32 AF XY: 0.169 AC XY: 12602 AN XY: 74422

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.225

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.193

Alfa AF: 0.107 Hom.: 157

Bravo AF: 0.177

Asia WGS AF: 0.0710 AC: 249 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.7
DANN	Benign	0.81

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: rs8191542; hg19: chr8-11629809;