Genetic Variant NEIL1:c.435-822_435-818delTTTTT (chr15-75351274-CTTTTT-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.100-12_100-8delTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000288 in 360,842 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000074 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00040 ( 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.435-822_435-818delTTTTT	intron	N/A	NP_078884.2	Q96FI4
NEIL1	NM_001256552.1		c.693-822_693-818delTTTTT	intron	N/A	NP_001243481.1	Q96FI4
NEIL1	NM_001352520.2		c.129-822_129-818delTTTTT	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_435-832delTTTTT	intron	N/A	ENSP00000347170.4	Q96FI4
NEIL1	ENST00000569035.5	TSL:1	c.435-836_435-832delTTTTT	intron	N/A	ENSP00000455730.1	Q96FI4
NEIL1	ENST00000866915.1		c.435-836_435-832delTTTTT	intron	N/A	ENSP00000536974.1

Frequencies

GnomAD3 genomes

AF:

0.0000743

AC:

AN:

121144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000601

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000101

Gnomad OTH

AF:

0.000617

GnomAD4 exome

AF:

0.000396

AC:

AN:

239698

Hom.:

AF XY:

0.000261

AC XY:

AN XY:

138010

show subpopulations

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

African (AFR)

AF:

0.00144

AC:

AN:

5542

American (AMR)

AF:

0.000606

AC:

AN:

16494

Ashkenazi Jewish (ASJ)

AF:

0.000387

AC:

AN:

7754

East Asian (EAS)

AF:

0.000488

AC:

AN:

8198

South Asian (SAS)

AF:

0.000281

AC:

AN:

46258

European-Finnish (FIN)

AF:

0.000418

AC:

AN:

9560

Middle Eastern (MID)

AF:

0.00119

AC:

AN:

842

European-Non Finnish (NFE)

AF:

0.000359

AC:

AN:

133874

Other (OTH)

AF:

0.000358

AC:

AN:

11176

⚠️ 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: 0.269

Heterozygous variant carriers

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:

0.0000743

AC:

AN:

121144

Hom.:

Cov.:

AF XY:

0.0000710

AC XY:

AN XY:

56372

show subpopulations

African (AFR)

AF:

0.0000601

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:

0.00

AC:

AN:

3614

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4128

Middle Eastern (MID)

AF:

0.00

AC:

AN:

246

European-Non Finnish (NFE)

AF:

0.000101

AC:

AN:

59238

Other (OTH)

AF:

0.000617

AC:

AN:

1622

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

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

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

Publications

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15-75351274-CTTTTTTTTT-CTTTT

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