chr4-177366124-A-G

Position:

• chr4-177366124-A-G

Variant summary

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

The XM_047415894.1(NEIL3):​c.*1205+2448A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.831 in 152,102 control chromosomes in the GnomAD database, including 53,455 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 0.83 (53455 hom., cov: 33)
• Consequence: NEIL3 XM_047415894.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.321

Genes affected

NEIL3 (HGNC:24573): (nei like DNA glycosylase 3) NEIL3 belongs to a class of DNA glycosylases homologous to the bacterial Fpg/Nei family. These glycosylases initiate the first step in base excision repair by cleaving bases damaged by reactive oxygen species and introducing a DNA strand break via the associated lyase reaction (Bandaru et al., 2002 [PubMed 12509226]).[supplied by OMIM, Mar 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.898 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEIL3	XM_047415894.1	c.*1205+2448A>G		intron_variant			XP_047271850.1
		n.177366124A>G		intergenic_region
LOC105377558	XR_001741926.2	n.37-4752T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.832 AC: 126420 AN: 151984 Hom.: 53446 Cov.: 33

Gnomad AFR AF: 0.669

Gnomad AMI AF: 0.965

Gnomad AMR AF: 0.870

Gnomad ASJ AF: 0.836

Gnomad EAS AF: 0.854

Gnomad SAS AF: 0.786

Gnomad FIN AF: 0.942

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.904

Gnomad OTH AF: 0.840

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.831 AC: 126470 AN: 152102 Hom.: 53455 Cov.: 33 AF XY: 0.832 AC XY: 61827 AN XY: 74334

Gnomad4 AFR AF: 0.668

Gnomad4 AMR AF: 0.870

Gnomad4 ASJ AF: 0.836

Gnomad4 EAS AF: 0.853

Gnomad4 SAS AF: 0.784

Gnomad4 FIN AF: 0.942

Gnomad4 NFE AF: 0.904

Gnomad4 OTH AF: 0.841

Alfa AF: 0.869 Hom.: 15946

Bravo AF: 0.822

Asia WGS AF: 0.819 AC: 2849 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.0
DANN	Benign	0.72

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7689397; hg19: chr4-178287278;