rs1043180

Variant names:

• chr8-11787312-C-T
• rs1043180
• NM_145043.4:c.*1039C>T

Variant summary

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

The NM_145043.4(NEIL2):​c.*1039C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0775 in 152,720 control chromosomes in the GnomAD database, including 616 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 0.077 (616 hom., cov: 32)
  • Exomes 𝑓: 0.098 (0 hom.)
• Consequence: NEIL2 NM_145043.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0570

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]

LOC105379243 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEIL2	NM_145043.4	c.*1039C>T		3_prime_UTR_variant	Exon 5 of 5	ENST00000284503.7	NP_659480.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEIL2	ENST00000284503.7	c.*1039C>T		3_prime_UTR_variant	Exon 5 of 5	2	NM_145043.4	ENSP00000284503.6
NEIL2	ENST00000436750.7	c.*1039C>T		3_prime_UTR_variant	Exon 5 of 5	1		ENSP00000394023.2
NEIL2	ENST00000455213.6	c.*1039C>T		3_prime_UTR_variant	Exon 6 of 6	5		ENSP00000397538.2
NEIL2	ENST00000403422.7	c.*1039C>T		3_prime_UTR_variant	Exon 4 of 4	2		ENSP00000384070.3

Frequencies

GnomAD3 genomes AF: 0.0776 AC: 11802 AN: 152154 Hom.: 617 Cov.: 32

Gnomad AFR AF: 0.0224

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.0860

Gnomad ASJ AF: 0.0743

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0487

Gnomad FIN AF: 0.0886

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.0766

GnomAD4 exome AF: 0.0982 AC: 44 AN: 448 Hom.: 0 Cov.: 0 AF XY: 0.0789 AC XY: 21 AN XY: 266

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0958

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.0775 AC: 11799 AN: 152272 Hom.: 616 Cov.: 32 AF XY: 0.0752 AC XY: 5599 AN XY: 74442

Gnomad4 AFR AF: 0.0223

Gnomad4 AMR AF: 0.0860

Gnomad4 ASJ AF: 0.0743

Gnomad4 EAS AF: 0.000964

Gnomad4 SAS AF: 0.0489

Gnomad4 FIN AF: 0.0886

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.0753

Alfa AF: 0.107 Hom.: 1341

Bravo AF: 0.0750

Asia WGS AF: 0.0250 AC: 87 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.6
DANN	Benign	0.49

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: rs1043180; hg19: chr8-11644821;