Genetic Variant NEIL1:c.435-818delT (chr15-75351274-CT-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_001352519.2(NEIL1):c.100-8delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.016 ( 8 hom., cov: 0)

Exomes 𝑓: 0.14 ( 0 hom. )

Consequence

NEIL1
NM_001352519.2 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0155 (1882/121106) while in subpopulation SAS AF = 0.0294 (106/3600). AF 95% confidence interval is 0.0249. There are 8 homozygotes in GnomAd4. There are 898 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 8 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.435-818delT	intron	N/A	NP_078884.2	Q96FI4
NEIL1	NM_001256552.1		c.693-818delT	intron	N/A	NP_001243481.1	Q96FI4
NEIL1	NM_001352520.2		c.129-818delT	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.435-836delT	intron	N/A	ENSP00000347170.4	Q96FI4
NEIL1	ENST00000569035.5	TSL:1	c.435-836delT	intron	N/A	ENSP00000455730.1	Q96FI4
NEIL1	ENST00000866915.1		c.435-836delT	intron	N/A	ENSP00000536974.1

Frequencies

GnomAD3 genomes

AF:

0.0155

AC:

1883

AN:

121112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00926

Gnomad AMI

AF:

0.0111

Gnomad AMR

AF:

0.0158

Gnomad ASJ

AF:

0.00963

Gnomad EAS

AF:

0.00102

Gnomad SAS

AF:

0.0296

Gnomad FIN

AF:

0.0116

Gnomad MID

AF:

0.0122

Gnomad NFE

AF:

0.0196

Gnomad OTH

AF:

0.0222

GnomAD4 exome

AF:

0.141

AC:

30839

AN:

219222

Hom.:

Cov.:

AF XY:

0.140

AC XY:

17559

AN XY:

125858

show subpopulations

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

African (AFR)

AF:

0.176

AC:

933

AN:

5304

American (AMR)

AF:

0.142

AC:

2164

AN:

15202

Ashkenazi Jewish (ASJ)

AF:

0.131

AC:

953

AN:

7262

East Asian (EAS)

AF:

0.125

AC:

956

AN:

7618

South Asian (SAS)

AF:

0.124

AC:

5169

AN:

41836

European-Finnish (FIN)

AF:

0.133

AC:

1158

AN:

8728

Middle Eastern (MID)

AF:

0.146

AC:

114

AN:

782

European-Non Finnish (NFE)

AF:

0.146

AC:

17875

AN:

122236

Other (OTH)

AF:

0.148

AC:

1517

AN:

10254

⚠️ 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: 0.272

Heterozygous variant carriers

2966

5932

8897

11863

14829

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

138

276

414

552

690

<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:

0.0155

AC:

1882

AN:

121106

Hom.:

Cov.:

AF XY:

0.0159

AC XY:

898

AN XY:

56372

show subpopulations

African (AFR)

AF:

0.00925

AC:

308

AN:

33292

American (AMR)

AF:

0.0159

AC:

178

AN:

11190

Ashkenazi Jewish (ASJ)

AF:

0.00963

AC:

AN:

3114

East Asian (EAS)

AF:

0.00102

AC:

AN:

3904

South Asian (SAS)

AF:

0.0294

AC:

106

AN:

3600

European-Finnish (FIN)

AF:

0.0116

AC:

AN:

4126

Middle Eastern (MID)

AF:

0.0133

AC:

AN:

226

European-Non Finnish (NFE)

AF:

0.0196

AC:

1160

AN:

59204

Other (OTH)

AF:

0.0220

AC:

AN:

1636

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.430

Heterozygous variant carriers

133

200

266

333

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.00273

Hom.:

282

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.065

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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