15-75351418-G-T

Position:

• chr15-75351418-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024608.4(NEIL1):​c.435-693G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 375,086 control chromosomes in the GnomAD database, including 44,096 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.44 (15386 hom., cov: 28)
  • Exomes 𝑓: 0.50 (28710 hom.)
• Consequence: NEIL1 NM_024608.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.54

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEIL1	NM_024608.4	c.435-693G>T		intron_variant		ENST00000355059.9	NP_078884.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEIL1	ENST00000355059.9	c.435-693G>T		intron_variant		2	NM_024608.4	ENSP00000347170.4

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66551 AN: 151292 Hom.: 15390 Cov.: 28

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.551

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.446

GnomAD4 exome AF: 0.503 AC: 112431 AN: 223676 Hom.: 28710 Cov.: 0 AF XY: 0.508 AC XY: 64201 AN XY: 126504

Gnomad4 AFR exome AF: 0.277

Gnomad4 AMR exome AF: 0.615

Gnomad4 ASJ exome AF: 0.475

Gnomad4 EAS exome AF: 0.550

Gnomad4 SAS exome AF: 0.553

Gnomad4 FIN exome AF: 0.487

Gnomad4 NFE exome AF: 0.486

Gnomad4 OTH exome AF: 0.487

GnomAD4 genome AF: 0.440 AC: 66564 AN: 151410 Hom.: 15386 Cov.: 28 AF XY: 0.441 AC XY: 32637 AN XY: 73976

Gnomad4 AFR AF: 0.296

Gnomad4 AMR AF: 0.552

Gnomad4 ASJ AF: 0.455

Gnomad4 EAS AF: 0.526

Gnomad4 SAS AF: 0.543

Gnomad4 FIN AF: 0.476

Gnomad4 NFE AF: 0.483

Gnomad4 OTH AF: 0.440

Alfa AF: 0.459 Hom.: 3423

Bravo AF: 0.440

Asia WGS AF: 0.523 AC: 1821 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.13
DANN	Benign	0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7182283; hg19: chr15-75643759;