Genetic Variant NEIL1:c.435-823_435-818dupTTTTTT (chr15-75351274-C-CTTTTTT) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001352519.2(NEIL1):c.100-13_100-8dupTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00016 ( 1 hom., cov: 0)

Exomes 𝑓: 0.00088 ( 3 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: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 3 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.435-823_435-818dupTTTTTT	intron	N/A	NP_078884.2	Q96FI4
NEIL1	NM_001256552.1		c.693-823_693-818dupTTTTTT	intron	N/A	NP_001243481.1	Q96FI4
NEIL1	NM_001352520.2		c.129-823_129-818dupTTTTTT	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_435-836insTTTTTT	intron	N/A	ENSP00000347170.4	Q96FI4
NEIL1	ENST00000569035.5	TSL:1	c.435-837_435-836insTTTTTT	intron	N/A	ENSP00000455730.1	Q96FI4
NEIL1	ENST00000866915.1		c.435-837_435-836insTTTTTT	intron	N/A	ENSP00000536974.1

Frequencies

GnomAD3 genomes

AF:

0.000165

AC:

AN:

121146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000301

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000179

Gnomad ASJ

AF:

0.000321

Gnomad EAS

AF:

0.00204

Gnomad SAS

AF:

0.000830

Gnomad FIN

AF:

0.000242

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000338

Gnomad OTH

AF:

0.00123

GnomAD4 exome

AF:

0.000882

AC:

212

AN:

240492

Hom.:

Cov.:

AF XY:

0.000759

AC XY:

105

AN XY:

138428

show subpopulations

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

African (AFR)

AF:

0.000537

AC:

AN:

5582

American (AMR)

AF:

0.00351

AC:

AN:

16520

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

7800

East Asian (EAS)

AF:

0.0103

AC:

AN:

8180

South Asian (SAS)

AF:

0.000668

AC:

AN:

46386

European-Finnish (FIN)

AF:

0.000939

AC:

AN:

9582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

846

European-Non Finnish (NFE)

AF:

0.000127

AC:

AN:

134376

Other (OTH)

AF:

0.000891

AC:

AN:

11220

⚠️ 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: 0.353

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:

0.000157

AC:

AN:

121140

Hom.:

Cov.:

AF XY:

0.000160

AC XY:

AN XY:

56386

show subpopulations

African (AFR)

AF:

0.0000300

AC:

AN:

33298

American (AMR)

AF:

0.000179

AC:

AN:

11192

Ashkenazi Jewish (ASJ)

AF:

0.000321

AC:

AN:

3116

East Asian (EAS)

AF:

0.00179

AC:

AN:

3904

South Asian (SAS)

AF:

0.000833

AC:

AN:

3602

European-Finnish (FIN)

AF:

0.000242

AC:

AN:

4128

Middle Eastern (MID)

AF:

0.00

AC:

AN:

226

European-Non Finnish (NFE)

AF:

0.0000338

AC:

AN:

59224

Other (OTH)

AF:

0.00122

AC:

AN:

1636

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

-0.065

Splicing

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

Publications

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15-75351274-CTTTTTTTTT-CTTTTTTTTTTTTTTT

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