Genetic Variant NEIL1:c.435-822_435-818delTTTTT (chr15-75351274-CTTTTT-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

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

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 made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEIL1	NM_024608.4 link	c.435-822_435-818delTTTTT		intron_variant	Intron 2 of 9	ENST00000355059.9	NP_078884.2	Q96FI4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEIL1	ENST00000355059.9 link	c.435-836_435-832delTTTTT		intron_variant	Intron 2 of 9	2	NM_024608.4	ENSP00000347170.4		Q96FI4

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

Gnomad4 AFR exome

AF:

0.00144

Gnomad4 AMR exome

AF:

0.000606

Gnomad4 ASJ exome

AF:

0.000387

Gnomad4 EAS exome

AF:

0.000488

Gnomad4 SAS exome

AF:

0.000281

Gnomad4 FIN exome

AF:

0.000418

Gnomad4 NFE exome

AF:

0.000359

Gnomad4 OTH exome

AF:

0.000358

GnomAD4 genome

AF:

0.0000743

AC:

AN:

121144

Hom.:

Cov.:

AF XY:

0.0000710

AC XY:

AN XY:

56372

show subpopulations

Gnomad4 AFR

AF:

0.0000601

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000101

Gnomad4 OTH

AF:

0.000617

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over