Genetic Variant NEIL1:p.Ala49Gly (chr15-75349051-C-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_024608.4(NEIL1):c.146C>G(p.Ala49Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000713 in 1,613,548 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0012 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00066 ( 19 hom. )

Consequence

NEIL1
NM_024608.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 7.11

Publications

3 publications found

Variant links:

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]

NEIL1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0044881403).

BP6

Variant 15-75349051-C-G is Benign according to our data. Variant chr15-75349051-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 771476.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.000662 (968/1461168) while in subpopulation AMR AF = 0.0196 (876/44724). AF 95% confidence interval is 0.0185. There are 19 homozygotes in GnomAdExome4. There are 405 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024608.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NEIL1	NM_024608.4	MANE Select	c.146C>G	p.Ala49Gly	missense	Exon 2 of 10	NP_078884.2	Q96FI4
NEIL1	NM_001256552.1		c.404C>G	p.Ala135Gly	missense	Exon 2 of 10	NP_001243481.1	Q96FI4
NEIL1	NM_001352519.2		c.-190C>G		5_prime_UTR	Exon 2 of 6	NP_001339448.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NEIL1	ENST00000355059.9	TSL:2 MANE Select	c.146C>G	p.Ala49Gly	missense	Exon 2 of 10	ENSP00000347170.4	Q96FI4
NEIL1	ENST00000569035.5	TSL:1	c.146C>G	p.Ala49Gly	missense	Exon 2 of 10	ENSP00000455730.1	Q96FI4
NEIL1	ENST00000866915.1		c.146C>G	p.Ala49Gly	missense	Exon 2 of 9	ENSP00000536974.1

Frequencies

GnomAD3 genomes

AF:

0.00118

AC:

179

AN:

152262

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0110

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000955

GnomAD2 exomes

AF:

0.00291

AC:

730

AN:

250550

AF XY:

0.00229

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.0206

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.000662

AC:

968

AN:

1461168

Hom.:

Cov.:

AF XY:

0.000557

AC XY:

405

AN XY:

726916

show subpopulations

African (AFR)

AF:

0.000119

AC:

AN:

33480

American (AMR)

AF:

0.0196

AC:

876

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.000104

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52850

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000369

AC:

AN:

1111886

Other (OTH)

AF:

0.000596

AC:

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

142

213

284

355

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00120

AC:

183

AN:

152380

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

102

AN XY:

74518

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

41600

American (AMR)

AF:

0.0112

AC:

172

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68036

Other (OTH)

AF:

0.000945

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000118

Hom.:

Bravo

AF:

0.00220

ExAC

AF:

0.00252

AC:

306

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.24

Eigen

Benign

0.036

Eigen_PC

Benign

0.058

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.92

MetaRNN

Benign

0.0045

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.7

PhyloP100

7.1

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.23

Sift

Benign

0.074

Sift4G

Benign

0.12

Polyphen

0.51

Vest4

0.42

MVP

0.41

MPC

0.44

ClinPred

0.056

GERP RS

5.4

Varity_R

0.50

gMVP

0.66

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over