rs804267

Variant names:

• chr8-11771732-G-A
• rs804267
• NM_145043.4:c.138+147G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-11771732-G-A
• chr8-11771732-G-C
• chr8-11771732-G-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.138+147G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 742,908 control chromosomes in the GnomAD database, including 172,273 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 0.64 (32004 hom., cov: 31)
  • Exomes 𝑓: 0.68 (140269 hom.)
• Consequence: NEIL2 NM_145043.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.182
• Publications: 20 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]

ACMG classification

Our verdict: Benign. The variant received -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 = 0.948 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEIL2	NM_145043.4	MANE Select	c.138+147G>A		intron	N/A	NP_659480.1	Q969S2-1
	NEIL2	NM_001135746.3		c.138+147G>A		intron	N/A	NP_001129218.1	Q969S2-1
	NEIL2	NM_001349442.2		c.138+147G>A		intron	N/A	NP_001336371.1	Q969S2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEIL2	ENST00000284503.7	TSL:2 MANE Select	c.138+147G>A		intron	N/A	ENSP00000284503.6	Q969S2-1
	NEIL2	ENST00000436750.7	TSL:1	c.138+147G>A		intron	N/A	ENSP00000394023.2	Q969S2-1
	NEIL2	ENST00000455213.6	TSL:5	c.138+147G>A		intron	N/A	ENSP00000397538.2	Q969S2-1

Frequencies

GnomAD3 genomes AF: 0.637 AC: 96776 AN: 151916 Hom.: 31994 Cov.: 31

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.700

Gnomad AMR AF: 0.744

Gnomad ASJ AF: 0.545

Gnomad EAS AF: 0.970

Gnomad SAS AF: 0.760

Gnomad FIN AF: 0.742

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.641

GnomAD4 exome AF: 0.680 AC: 401792 AN: 590874 Hom.: 140269 AF XY: 0.682 AC XY: 209891 AN XY: 307924

African (AFR) AF: 0.441 AC: 6985 AN: 15840

American (AMR) AF: 0.789 AC: 16342 AN: 20706

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 8192 AN: 14764

East Asian (EAS) AF: 0.975 AC: 31982 AN: 32786

South Asian (SAS) AF: 0.742 AC: 37894 AN: 51068

European-Finnish (FIN) AF: 0.718 AC: 23493 AN: 32714

Middle Eastern (MID) AF: 0.550 AC: 1925 AN: 3502

European-Non Finnish (NFE) AF: 0.655 AC: 254324 AN: 388492

Other (OTH) AF: 0.666 AC: 20655 AN: 31002

GnomAD4 genome AF: 0.637 AC: 96817 AN: 152034 Hom.: 32004 Cov.: 31 AF XY: 0.645 AC XY: 47904 AN XY: 74316

African (AFR) AF: 0.459 AC: 19003 AN: 41436

American (AMR) AF: 0.745 AC: 11382 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.545 AC: 1891 AN: 3468

East Asian (EAS) AF: 0.970 AC: 5015 AN: 5170

South Asian (SAS) AF: 0.759 AC: 3660 AN: 4822

European-Finnish (FIN) AF: 0.742 AC: 7850 AN: 10586

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.675 AC: 45860 AN: 67958

Other (OTH) AF: 0.646 AC: 1361 AN: 2106

Alfa AF: 0.665 Hom.: 145226

Bravo AF: 0.632

Asia WGS AF: 0.827 AC: 2875 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.6
DANN	Benign	0.91
PhyloP100		-0.18
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: rs804267; hg19: chr8-11629241;