Genetic Variant NEIL1:c.435-821_435-818delTTTT (chr15-75351274-CTTTT-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001352519.2(NEIL1):c.100-11_100-8delTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00126 in 357,494 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000066 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0019 ( 0 hom. )

Consequence

NEIL1
NM_001352519.2 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.212

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: Uncertain_significance. The variant received 0 ACMG points.

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.435-821_435-818delTTTT	intron	N/A	NP_078884.2	Q96FI4
NEIL1	NM_001256552.1		c.693-821_693-818delTTTT	intron	N/A	NP_001243481.1	Q96FI4
NEIL1	NM_001352520.2		c.129-821_129-818delTTTT	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.435-836_435-833delTTTT	intron	N/A	ENSP00000347170.4	Q96FI4
NEIL1	ENST00000569035.5	TSL:1	c.435-836_435-833delTTTT	intron	N/A	ENSP00000455730.1	Q96FI4
NEIL1	ENST00000866915.1		c.435-836_435-833delTTTT	intron	N/A	ENSP00000536974.1

Frequencies

GnomAD3 genomes

AF:

0.0000660

AC:

AN:

121124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000902

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000277

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000675

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00187

AC:

442

AN:

236370

Hom.:

AF XY:

0.00171

AC XY:

233

AN XY:

136112

show subpopulations

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

African (AFR)

AF:

0.00369

AC:

AN:

5416

American (AMR)

AF:

0.00197

AC:

AN:

16234

Ashkenazi Jewish (ASJ)

AF:

0.00249

AC:

AN:

7640

East Asian (EAS)

AF:

0.00617

AC:

AN:

8106

South Asian (SAS)

AF:

0.00107

AC:

AN:

45628

European-Finnish (FIN)

AF:

0.00149

AC:

AN:

9426

Middle Eastern (MID)

AF:

0.00120

AC:

AN:

836

European-Non Finnish (NFE)

AF:

0.00178

AC:

235

AN:

132050

Other (OTH)

AF:

0.00199

AC:

AN:

11034

⚠️ 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: 0.250

Heterozygous variant carriers

131

197

262

328

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000660

AC:

AN:

121124

Hom.:

Cov.:

AF XY:

0.0000710

AC XY:

AN XY:

56362

show subpopulations

African (AFR)

AF:

0.0000902

AC:

AN:

33262

American (AMR)

AF:

0.00

AC:

AN:

11188

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3114

East Asian (EAS)

AF:

0.00

AC:

AN:

3918

South Asian (SAS)

AF:

0.000277

AC:

AN:

3614

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4120

Middle Eastern (MID)

AF:

0.00

AC:

AN:

246

European-Non Finnish (NFE)

AF:

0.0000675

AC:

AN:

59226

Other (OTH)

AF:

0.00

AC:

AN:

1622

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

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:

0.00

Hom.:

282

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.21

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

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