rs10013040

Variant names:

• chr4-177309998-C-A
• rs10013040
• NM_018248.3:c.45C>A

Your query was ambiguous. Multiple possible variants found:

• chr4-177309998-C-A
• chr4-177309998-C-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_018248.3(NEIL3):​c.45C>A​(p.Arg15Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 1,609,634 control chromosomes in the GnomAD database, including 38,459 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (3021 hom., cov: 33)
  • Exomes 𝑓: 0.22 (35438 hom.)
• Consequence: NEIL3 NM_018248.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.224
• Publications: 15 publications found

Genes affected

NEIL3 (HGNC:24573): (nei like DNA glycosylase 3) NEIL3 belongs to a class of DNA glycosylases homologous to the bacterial Fpg/Nei family. These glycosylases initiate the first step in base excision repair by cleaving bases damaged by reactive oxygen species and introducing a DNA strand break via the associated lyase reaction (Bandaru et al., 2002 [PubMed 12509226]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 4-177309998-C-A is Benign according to our data. Variant chr4-177309998-C-A is described in ClinVar as Benign. ClinVar VariationId is 2688445.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.224 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018248.3. 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
	NEIL3	NM_018248.3	MANE Select	c.45C>A	p.Arg15Arg	synonymous	Exon 1 of 10	NP_060718.3	Q8TAT5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEIL3	ENST00000264596.4	TSL:1 MANE Select	c.45C>A	p.Arg15Arg	synonymous	Exon 1 of 10	ENSP00000264596.3	Q8TAT5
	NEIL3	ENST00000513321.1	TSL:1	n.45C>A		non_coding_transcript_exon	Exon 1 of 4	ENSP00000424735.1	D6RAV1
	NEIL3	ENST00000905043.1		c.45C>A	p.Arg15Arg	synonymous	Exon 1 of 10	ENSP00000575102.1

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29781 AN: 152044 Hom.: 3017 Cov.: 33

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.208

GnomAD2 exomes AF: 0.201 AC: 49607 AN: 246254 AF XY: 0.205

Gnomad AFR exome AF: 0.146

Gnomad AMR exome AF: 0.178

Gnomad ASJ exome AF: 0.229

Gnomad EAS exome AF: 0.131

Gnomad FIN exome AF: 0.190

Gnomad NFE exome AF: 0.225

Gnomad OTH exome AF: 0.225

GnomAD4 exome AF: 0.219 AC: 318548 AN: 1457472 Hom.: 35438 Cov.: 33 AF XY: 0.219 AC XY: 158798 AN XY: 724990

African (AFR) AF: 0.151 AC: 5011 AN: 33254

American (AMR) AF: 0.181 AC: 8056 AN: 44390

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 6113 AN: 26012

East Asian (EAS) AF: 0.155 AC: 6125 AN: 39428

South Asian (SAS) AF: 0.202 AC: 17299 AN: 85812

European-Finnish (FIN) AF: 0.191 AC: 10175 AN: 53320

Middle Eastern (MID) AF: 0.285 AC: 1335 AN: 4684

European-Non Finnish (NFE) AF: 0.227 AC: 251515 AN: 1110406

Other (OTH) AF: 0.215 AC: 12919 AN: 60166

GnomAD4 genome AF: 0.196 AC: 29809 AN: 152162 Hom.: 3021 Cov.: 33 AF XY: 0.195 AC XY: 14482 AN XY: 74402

African (AFR) AF: 0.151 AC: 6269 AN: 41542

American (AMR) AF: 0.199 AC: 3042 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 795 AN: 3470

East Asian (EAS) AF: 0.142 AC: 734 AN: 5156

South Asian (SAS) AF: 0.202 AC: 975 AN: 4826

European-Finnish (FIN) AF: 0.189 AC: 2002 AN: 10588

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.225 AC: 15303 AN: 67966

Other (OTH) AF: 0.206 AC: 436 AN: 2116

Alfa AF: 0.212 Hom.: 10947

Bravo AF: 0.192

Asia WGS AF: 0.177 AC: 617 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	12
DANN	Benign	0.92
PhyloP100		0.22
PromoterAI		0.029	Neutral
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: rs10013040; hg19: chr4-178231152; COSMIC: COSV52812556;