15-75348082-C-T

Position:

• chr15-75348082-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024608.4(NEIL1):​c.-23+609C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 1,006,760 control chromosomes in the GnomAD database, including 31,790 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3572 hom., cov: 33)
  • Exomes 𝑓: 0.25 (28218 hom.)
• Consequence: NEIL1 NM_024608.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -5.94

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 15-75348082-C-T is Benign according to our data. Variant chr15-75348082-C-T is described in ClinVar as [Benign]. Clinvar id is 1280215.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEIL1	NM_024608.4	c.-23+609C>T		intron_variant		ENST00000355059.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEIL1	ENST00000355059.9	c.-23+609C>T		intron_variant		2	NM_024608.4	P1

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30946 AN: 152030 Hom.: 3569 Cov.: 33

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.0231

Gnomad SAS AF: 0.0617

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.181

GnomAD4 exome AF: 0.251 AC: 214351 AN: 854612 Hom.: 28218 Cov.: 12 AF XY: 0.247 AC XY: 100365 AN XY: 406914

Gnomad4 AFR exome AF: 0.160

Gnomad4 AMR exome AF: 0.0934

Gnomad4 ASJ exome AF: 0.144

Gnomad4 EAS exome AF: 0.0244

Gnomad4 SAS exome AF: 0.0681

Gnomad4 FIN exome AF: 0.274

Gnomad4 NFE exome AF: 0.269

Gnomad4 OTH exome AF: 0.212

GnomAD4 genome AF: 0.203 AC: 30950 AN: 152148 Hom.: 3572 Cov.: 33 AF XY: 0.201 AC XY: 14922 AN XY: 74402

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.0227

Gnomad4 SAS AF: 0.0611

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.257

Gnomad4 OTH AF: 0.178

Alfa AF: 0.239 Hom.: 605

Bravo AF: 0.191

Asia WGS AF: 0.0490 AC: 172 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 20, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.66
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs79244935; hg19: chr15-75640423;