rs5745906

Variant names:

• chr15-75349153-G-A
• rs5745906
• NM_024608.4:c.248G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-75349153-G-A
• chr15-75349153-G-C

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 1P and 8B. PP3 BP4_Strong BS2

The NM_024608.4(NEIL1):​c.248G>A​(p.Gly83Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,609,500 control chromosomes in the GnomAD database, including 4 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.00077 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (4 hom.)
• Consequence: NEIL1 NM_024608.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.14

Genes affected

NEIL1 (HGNC:18448): (nei like DNA glycosylase 1) This gene is a member of the Nei endonuclease VIII-like gene family which encodes DNA glycosylases. The encoded enzyme participates in the DNA repair pathway by initiating base excision repair by removing damaged bases, primarily oxidized pyrimidines. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• PP3: Multiple lines of computational evidence support a deleterious effect 9: AlphaMissense, BayesDel_noAF, Cadd, Eigen, MutationAssessor, phyloP100way_vertebrate, PROVEAN, REVEL, REVEL [when max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]
• BP4: Computational evidence support a benign effect (MetaRNN=0.04553938).
• BS2: High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEIL1	NM_024608.4	c.248G>A	p.Gly83Asp	missense_variant	Exon 2 of 10	ENST00000355059.9	NP_078884.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEIL1	ENST00000355059.9	c.248G>A	p.Gly83Asp	missense_variant	Exon 2 of 10	2	NM_024608.4	ENSP00000347170.4

Frequencies

GnomAD3 genomes AF: 0.000775 AC: 118 AN: 152258 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.00950

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000970

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.00122 AC: 300 AN: 246258 AF XY: 0.00111

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00154

Gnomad ASJ exome AF: 0.00967

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000108

Gnomad NFE exome AF: 0.00119

Gnomad OTH exome AF: 0.00230

GnomAD4 exome AF: 0.00106 AC: 1547 AN: 1457124 Hom.: 4 Cov.: 31 AF XY: 0.00102 AC XY: 736 AN XY: 725094

Gnomad4 AFR exome AF: 0.00 AC: 0 AN: 33462

Gnomad4 AMR exome AF: 0.00159 AC: 71 AN: 44718

Gnomad4 ASJ exome AF: 0.0108 AC: 282 AN: 26116

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39694

Gnomad4 SAS exome AF: 0.00 AC: 0 AN: 86224

Gnomad4 FIN exome AF: 0.000244 AC: 12 AN: 49184

Gnomad4 NFE exome AF: 0.000991 AC: 1102 AN: 1111874

Gnomad4 Remaining exome AF: 0.00131 AC: 79 AN: 60332

GnomAD4 genome AF: 0.000768 AC: 117 AN: 152376 Hom.: 0 Cov.: 33 AF XY: 0.000738 AC XY: 55 AN XY: 74516

Gnomad4 AFR AF: 0.000120 AC: 0.000120192 AN: 0.000120192

Gnomad4 AMR AF: 0.000653 AC: 0.000653083 AN: 0.000653083

Gnomad4 ASJ AF: 0.00950 AC: 0.00950461 AN: 0.00950461

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.000188 AC: 0.000188218 AN: 0.000188218

Gnomad4 NFE AF: 0.000955 AC: 0.000955405 AN: 0.000955405

Gnomad4 OTH AF: 0.000947 AC: 0.00094697 AN: 0.00094697

Alfa AF: 0.00132 Hom.: 1

Bravo AF: 0.000861

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000228 AC: 1

ESP6500EA AF: 0.00175 AC: 15

ExAC AF: 0.00123 AC: 149

EpiCase AF: 0.000981

EpiControl AF: 0.000889

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Pathogenic	0.42
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.47	T;.;T;T;T;.;.;T
Eigen	Pathogenic	0.97
Eigen_PC	Pathogenic	0.88
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.94	.;D;D;.;D;D;D;D
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.046	T;T;T;T;T;T;T;T
MetaSVM	Pathogenic	0.86	D
MutationAssessor	Pathogenic	4.1	H;.;.;H;H;.;.;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-5.3	D;D;D;D;D;D;D;D
REVEL	Pathogenic	0.86
Sift	Pathogenic	0.0	D;D;D;D;D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;D;D
Polyphen		1.0	D;.;.;D;D;.;.;.
Vest4		0.94
MVP		0.95
MPC		0.78
ClinPred		0.22	T
GERP RS		5.4
Varity_R		0.95
gMVP		0.94
Mutation Taster		=16/84	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs5745906; hg19: chr15-75641494;