15-75351418-G-T

Variant names:

• chr15-75351418-G-T
• rs7182283
• NM_024608.4:c.435-693G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NEIL1	NM_024608.4	c.435-693G>T		intron_variant	Intron 2 of 9	ENST00000355059.9	NP_078884.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEIL1	ENST00000355059.9	c.435-693G>T		intron_variant	Intron 2 of 9	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

African (AFR) AF: 0.277 AC: 1514 AN: 5466

American (AMR) AF: 0.615 AC: 7925 AN: 12880

Ashkenazi Jewish (ASJ) AF: 0.475 AC: 2450 AN: 5160

East Asian (EAS) AF: 0.550 AC: 4728 AN: 8600

South Asian (SAS) AF: 0.553 AC: 24023 AN: 43470

European-Finnish (FIN) AF: 0.487 AC: 4398 AN: 9034

Middle Eastern (MID) AF: 0.411 AC: 915 AN: 2224

European-Non Finnish (NFE) AF: 0.486 AC: 61186 AN: 125984

Other (OTH) AF: 0.487 AC: 5292 AN: 10858

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

African (AFR) AF: 0.296 AC: 12183 AN: 41190

American (AMR) AF: 0.552 AC: 8383 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.455 AC: 1579 AN: 3470

East Asian (EAS) AF: 0.526 AC: 2691 AN: 5120

South Asian (SAS) AF: 0.543 AC: 2597 AN: 4784

European-Finnish (FIN) AF: 0.476 AC: 4986 AN: 10482

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.483 AC: 32752 AN: 67862

Other (OTH) AF: 0.440 AC: 924 AN: 2098

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
PhyloP100		-2.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7182283; hg19: chr15-75643759;