Genetic Variant NM_024608.4:c.435-822_435-818dupTTTTT (chr15-75351274-C-CTTTTT) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_024608.4(NEIL1):c.435-822_435-818dupTTTTT variant causes a 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 0.0044 ( 13 hom., cov: 0)

Exomes 𝑓: 0.0031 ( 0 hom. )

Consequence

NEIL1
NM_024608.4 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.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0686 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024608.4. 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_435-818dupTTTTT	intron	N/A	NP_078884.2	Q96FI4
NEIL1	NM_001256552.1		c.693-822_693-818dupTTTTT	intron	N/A	NP_001243481.1	Q96FI4
NEIL1	NM_001352520.2		c.129-822_129-818dupTTTTT	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_435-836insTTTTT	intron	N/A	ENSP00000347170.4	Q96FI4
NEIL1	ENST00000569035.5	TSL:1	c.435-837_435-836insTTTTT	intron	N/A	ENSP00000455730.1	Q96FI4
NEIL1	ENST00000866915.1		c.435-837_435-836insTTTTT	intron	N/A	ENSP00000536974.1

Frequencies

GnomAD3 genomes

AF:

0.00443

AC:

536

AN:

121102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000511

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0122

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0757

Gnomad SAS

AF:

0.00194

Gnomad FIN

AF:

0.00801

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000642

Gnomad OTH

AF:

0.00617

GnomAD4 exome

AF:

0.00313

AC:

752

AN:

240284

Hom.:

Cov.:

AF XY:

0.00289

AC XY:

400

AN XY:

138328

show subpopulations

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

African (AFR)

AF:

0.000358

AC:

AN:

5582

American (AMR)

AF:

0.0111

AC:

182

AN:

16458

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

7802

East Asian (EAS)

AF:

0.0377

AC:

307

AN:

8144

South Asian (SAS)

AF:

0.00168

AC:

AN:

46360

European-Finnish (FIN)

AF:

0.00953

AC:

AN:

9552

Middle Eastern (MID)

AF:

0.00

AC:

AN:

846

European-Non Finnish (NFE)

AF:

0.000432

AC:

AN:

134332

Other (OTH)

AF:

0.00303

AC:

AN:

11208

⚠️ 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: 0.373

Heterozygous variant carriers

109

136

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.00443

AC:

536

AN:

121096

Hom.:

Cov.:

AF XY:

0.00483

AC XY:

272

AN XY:

56356

show subpopulations

African (AFR)

AF:

0.000511

AC:

AN:

33298

American (AMR)

AF:

0.0122

AC:

137

AN:

11186

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3114

East Asian (EAS)

AF:

0.0757

AC:

294

AN:

3882

South Asian (SAS)

AF:

0.00194

AC:

AN:

3602

European-Finnish (FIN)

AF:

0.00801

AC:

AN:

4118

Middle Eastern (MID)

AF:

0.00

AC:

AN:

226

European-Non Finnish (NFE)

AF:

0.000642

AC:

AN:

59220

Other (OTH)

AF:

0.00611

AC:

AN:

1636

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.529

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:

0.00166

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

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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