Genetic Variant NM_024608.4:c.203C>A (chr15-75349108-C-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_024608.4(NEIL1):c.203C>A(p.Pro68His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000319 in 1,612,058 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00056 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00029 ( 5 hom. )

Consequence

NEIL1
NM_024608.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.40

Publications

8 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003751278).

BP6

Variant 15-75349108-C-A is Benign according to our data. Variant chr15-75349108-C-A is described in ClinVar as Benign. ClinVar VariationId is 782887.Status of the report is criteria_provided_single_submitter, 1 stars.

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.203C>A	p.Pro68His	missense	Exon 2 of 10	NP_078884.2	Q96FI4
NEIL1	NM_001256552.1		c.461C>A	p.Pro154His	missense	Exon 2 of 10	NP_001243481.1	Q96FI4
NEIL1	NM_001352519.2		c.-133C>A		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.203C>A	p.Pro68His	missense	Exon 2 of 10	ENSP00000347170.4	Q96FI4
NEIL1	ENST00000569035.5	TSL:1	c.203C>A	p.Pro68His	missense	Exon 2 of 10	ENSP00000455730.1	Q96FI4
NEIL1	ENST00000866915.1		c.203C>A	p.Pro68His	missense	Exon 2 of 9	ENSP00000536974.1

Frequencies

GnomAD3 genomes

AF:

0.000558

AC:

AN:

152258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0125

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00114

AC:

282

AN:

248408

AF XY:

0.00108

show subpopulations

Gnomad AFR exome

AF:

0.000250

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0144

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000656

GnomAD4 exome

AF:

0.000294

AC:

429

AN:

1459682

Hom.:

Cov.:

AF XY:

0.000288

AC XY:

209

AN XY:

726272

show subpopulations

African (AFR)

AF:

0.0000896

AC:

AN:

33470

American (AMR)

AF:

0.0000671

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00720

AC:

286

AN:

39696

South Asian (SAS)

AF:

0.000325

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51452

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5704

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1111904

Other (OTH)

AF:

0.00174

AC:

105

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

128

160

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:

0.000558

AC:

AN:

152376

Hom.:

Cov.:

AF XY:

0.000644

AC XY:

AN XY:

74522

show subpopulations

African (AFR)

AF:

0.000264

AC:

AN:

41592

American (AMR)

AF:

0.0000653

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.0125

AC:

AN:

5186

South Asian (SAS)

AF:

0.000828

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68034

Other (OTH)

AF:

0.00189

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.000580

Hom.:

Bravo

AF:

0.000514

ExAC

AF:

0.000997

AC:

121

Asia WGS

AF:

0.00664

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.44

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.12

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.80

MetaRNN

Benign

0.0038

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

PhyloP100

2.4

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.10

Sift

Benign

0.031

Sift4G

Benign

0.10

Polyphen

0.25

Vest4

0.18

MVP

0.62

MPC

0.70

ClinPred

0.037

GERP RS

5.4

Varity_R

0.40

gMVP

0.30

Mutation Taster

=99/1

polymorphism

(source)

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

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