chr8-11787312-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 21 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145043.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEIL2	NM_145043.4	MANE Select	c.*1039C>T		3_prime_UTR	Exon 5 of 5	NP_659480.1
	NEIL2	NM_001135746.3		c.*1039C>T		3_prime_UTR	Exon 5 of 5	NP_001129218.1
	NEIL2	NM_001349442.2		c.*1039C>T		3_prime_UTR	Exon 6 of 6	NP_001336371.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEIL2	ENST00000284503.7	TSL:2 MANE Select	c.*1039C>T		3_prime_UTR	Exon 5 of 5	ENSP00000284503.6
	NEIL2	ENST00000436750.7	TSL:1	c.*1039C>T		3_prime_UTR	Exon 5 of 5	ENSP00000394023.2
	NEIL2	ENST00000455213.6	TSL:5	c.*1039C>T		3_prime_UTR	Exon 6 of 6	ENSP00000397538.2

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.0958 AC: 41 AN: 428

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.167 AC: 2 AN: 12

Other (OTH) AF: 0.167 AC: 1 AN: 6

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

African (AFR) AF: 0.0223 AC: 928 AN: 41566

American (AMR) AF: 0.0860 AC: 1316 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0743 AC: 258 AN: 3472

East Asian (EAS) AF: 0.000964 AC: 5 AN: 5188

South Asian (SAS) AF: 0.0489 AC: 236 AN: 4824

European-Finnish (FIN) AF: 0.0886 AC: 939 AN: 10596

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7816 AN: 68008

Other (OTH) AF: 0.0753 AC: 159 AN: 2112

Alfa AF: 0.105 Hom.: 1807

Bravo AF: 0.0750

Asia WGS AF: 0.0250 AC: 87 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.6
DANN	Benign	0.49
PhyloP100		-0.057
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1043180; hg19: chr8-11644821;