Genetic Variant NEIL1:c.435-819_435-818dupTT (chr15-75351274-C-CTT) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP6BS2

The NM_001352519.2(NEIL1):c.100-9_100-8dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0085 ( 28 hom., cov: 0)

Exomes 𝑓: 0.033 ( 4 hom. )

Consequence

NEIL1
NM_001352519.2 splice_region, intron

Scores

Not classified

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.0650

Publications

0 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: Likely_benign. The variant received -5 ACMG points.

BP6

Variant 15-75351274-C-CTT is Benign according to our data. Variant chr15-75351274-C-CTT is described in ClinVar as Benign. ClinVar VariationId is 3037264.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 28 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001352519.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NEIL1	NM_024608.4	MANE Select	c.435-819_435-818dupTT	intron	N/A	NP_078884.2	Q96FI4
NEIL1	NM_001256552.1		c.693-819_693-818dupTT	intron	N/A	NP_001243481.1	Q96FI4
NEIL1	NM_001352520.2		c.129-819_129-818dupTT	intron	N/A	NP_001339449.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NEIL1	ENST00000355059.9	TSL:2 MANE Select	c.435-837_435-836insTT	intron	N/A	ENSP00000347170.4	Q96FI4
NEIL1	ENST00000569035.5	TSL:1	c.435-837_435-836insTT	intron	N/A	ENSP00000455730.1	Q96FI4
NEIL1	ENST00000866915.1		c.435-837_435-836insTT	intron	N/A	ENSP00000536974.1

Frequencies

GnomAD3 genomes

AF:

0.00852

AC:

1032

AN:

121120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00391

Gnomad AMI

AF:

0.00369

Gnomad AMR

AF:

0.00840

Gnomad ASJ

AF:

0.00514

Gnomad EAS

AF:

0.00357

Gnomad SAS

AF:

0.0138

Gnomad FIN

AF:

0.00339

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0117

Gnomad OTH

AF:

0.0123

GnomAD4 exome

AF:

0.0325

AC:

7639

AN:

235036

Hom.:

Cov.:

AF XY:

0.0320

AC XY:

4332

AN XY:

135366

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0216

AC:

119

AN:

5518

American (AMR)

AF:

0.0360

AC:

583

AN:

16188

Ashkenazi Jewish (ASJ)

AF:

0.0266

AC:

204

AN:

7664

East Asian (EAS)

AF:

0.0429

AC:

348

AN:

8114

South Asian (SAS)

AF:

0.0422

AC:

1896

AN:

44964

European-Finnish (FIN)

AF:

0.0276

AC:

258

AN:

9344

Middle Eastern (MID)

AF:

0.0288

AC:

AN:

834

European-Non Finnish (NFE)

AF:

0.0297

AC:

3903

AN:

131444

Other (OTH)

AF:

0.0277

AC:

304

AN:

10966

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.303

Heterozygous variant carriers

509

1019

1528

2038

2547

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

120

160

200

<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:

0.00851

AC:

1031

AN:

121114

Hom.:

Cov.:

AF XY:

0.00867

AC XY:

489

AN XY:

56374

show subpopulations

African (AFR)

AF:

0.00390

AC:

130

AN:

33292

American (AMR)

AF:

0.00840

AC:

AN:

11192

Ashkenazi Jewish (ASJ)

AF:

0.00514

AC:

AN:

3110

East Asian (EAS)

AF:

0.00359

AC:

AN:

3904

South Asian (SAS)

AF:

0.0136

AC:

AN:

3602

European-Finnish (FIN)

AF:

0.00339

AC:

AN:

4128

Middle Eastern (MID)

AF:

0.00

AC:

AN:

226

European-Non Finnish (NFE)

AF:

0.0117

AC:

691

AN:

59212

Other (OTH)

AF:

0.0122

AC:

AN:

1636

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.544

Heterozygous variant carriers

109

145

181

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00190

Hom.:

282

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

NEIL1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.065

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

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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