Variant 15-75349108-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 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

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:

NEIL1 (HGNC:):

NEIL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 782887.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEIL1	NM_024608.4 linkuse as main transcript	c.203C>A	p.Pro68His	missense_variant	2/10	ENST00000355059.9	NP_078884.2	Q96FI4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEIL1	ENST00000355059.9 linkuse as main transcript	c.203C>A	p.Pro68His	missense_variant	2/10	2	NM_024608.4	ENSP00000347170.4		Q96FI4

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

GnomAD3 exomes

AF:

0.00114

AC:

282

AN:

248408

Hom.:

AF XY:

0.00108

AC XY:

146

AN XY:

134804

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 SAS exome

AF:

0.000261

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

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00720

Gnomad4 SAS exome

AF:

0.000325

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00174

GnomAD4 genome

AF:

0.000558

AC:

AN:

152376

Hom.:

Cov.:

AF XY:

0.000644

AC XY:

AN XY:

74522

show subpopulations

Gnomad4 AFR

AF:

0.000264

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0125

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000566

Hom.:

Bravo

AF:

0.000514

ExAC

AF:

0.000997

AC:

121

Asia WGS

AF:

0.00664

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.44

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.12

T;.;T;T;T;.;.;T;.

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.80

.;T;T;.;T;T;T;T;T

MetaRNN

Benign

0.0038

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;.;.;L;L;.;.;.;.

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-2.4

N;D;D;N;N;D;D;D;D

REVEL

Benign

0.10

Sift

Benign

0.031

D;T;T;D;D;T;T;T;T

Sift4G

Benign

0.10

T;T;T;T;T;T;T;T;T

Polyphen

0.25

B;.;.;B;B;.;.;.;.

Vest4

0.18

MVP

0.62

MPC

0.70

ClinPred

0.037

GERP RS

5.4

Varity_R

0.40

gMVP

0.30

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over