rs5745925

Variant names:

• chr15-75353624-CCT-C
• rs5745925
• NM_024608.4:c.719-114_719-113delCT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_024608.4(NEIL1):​c.719-114_719-113delCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0682 in 1,130,302 control chromosomes in the GnomAD database, including 3,069 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.057 (315 hom., cov: 32)
  • Exomes 𝑓: 0.070 (2754 hom.)
• Consequence: NEIL1 NM_024608.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.98
• Publications: 15 publications found

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]

MIR631 (HGNC:32887): (microRNA 631) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 15-75353624-CCT-C is Benign according to our data. Variant chr15-75353624-CCT-C is described in ClinVar as Benign. ClinVar VariationId is 1281887.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEIL1	NM_024608.4	c.719-114_719-113delCT		intron_variant	Intron 5 of 9	ENST00000355059.9	NP_078884.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEIL1	ENST00000355059.9	c.719-114_719-113delCT		intron_variant	Intron 5 of 9	2	NM_024608.4	ENSP00000347170.4

Frequencies

GnomAD3 genomes AF: 0.0569 AC: 8651 AN: 152074 Hom.: 314 Cov.: 32

Gnomad AFR AF: 0.0240

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.0464

Gnomad ASJ AF: 0.0775

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0230

Gnomad FIN AF: 0.0859

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0800

Gnomad OTH AF: 0.0498

GnomAD2 exomes AF: 0.0589 AC: 14791 AN: 251262 AF XY: 0.0593

Gnomad AFR exome AF: 0.0225

Gnomad AMR exome AF: 0.0343

Gnomad ASJ exome AF: 0.0766

Gnomad EAS exome AF: 0.000272

Gnomad FIN exome AF: 0.0872

Gnomad NFE exome AF: 0.0816

Gnomad OTH exome AF: 0.0656

GnomAD4 exome AF: 0.0700 AC: 68487 AN: 978110 Hom.: 2754 AF XY: 0.0693 AC XY: 35121 AN XY: 506834

African (AFR) AF: 0.0221 AC: 530 AN: 23992

American (AMR) AF: 0.0356 AC: 1563 AN: 43878

Ashkenazi Jewish (ASJ) AF: 0.0803 AC: 1832 AN: 22824

East Asian (EAS) AF: 0.000164 AC: 6 AN: 36612

South Asian (SAS) AF: 0.0311 AC: 2359 AN: 75848

European-Finnish (FIN) AF: 0.0883 AC: 4661 AN: 52770

Middle Eastern (MID) AF: 0.0454 AC: 217 AN: 4782

European-Non Finnish (NFE) AF: 0.0811 AC: 54641 AN: 673564

Other (OTH) AF: 0.0611 AC: 2678 AN: 43840

GnomAD4 genome AF: 0.0568 AC: 8651 AN: 152192 Hom.: 315 Cov.: 32 AF XY: 0.0551 AC XY: 4099 AN XY: 74394

African (AFR) AF: 0.0239 AC: 994 AN: 41528

American (AMR) AF: 0.0463 AC: 708 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0775 AC: 269 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.0230 AC: 111 AN: 4826

European-Finnish (FIN) AF: 0.0859 AC: 910 AN: 10592

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0800 AC: 5437 AN: 67982

Other (OTH) AF: 0.0488 AC: 103 AN: 2110

Alfa AF: 0.0710 Hom.: 75

Bravo AF: 0.0527

Asia WGS AF: 0.0140 AC: 48 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 20, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.0
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs5745925; hg19: chr15-75645965; COSMIC: COSV51235898; COSMIC: COSV51235898;