15-75355623-G-C

Variant names:

• chr15-75355623-G-C
• rs4462560
• NM_024608.4:c.*589G>C

Variant summary

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

The NM_024608.4(NEIL1):​c.*589G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 369,712 control chromosomes in the GnomAD database, including 87,142 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 0.64 (32743 hom., cov: 30)
  • Exomes 𝑓: 0.70 (54399 hom.)
• Consequence: NEIL1 NM_024608.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.826

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]

MAN2C1 (HGNC:6827): (mannosidase alpha class 2C member 1) Predicted to enable alpha-mannosidase activity. Predicted to be involved in oligosaccharide catabolic process. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEIL1	NM_024608.4	c.*589G>C		3_prime_UTR_variant	Exon 10 of 10	ENST00000355059.9	NP_078884.2
MAN2C1	NM_006715.4	c.*283C>G		downstream_gene_variant		ENST00000267978.10	NP_006706.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEIL1	ENST00000355059.9	c.*589G>C		3_prime_UTR_variant	Exon 10 of 10	2	NM_024608.4	ENSP00000347170.4
MAN2C1	ENST00000267978.10	c.*283C>G		downstream_gene_variant		1	NM_006715.4	ENSP00000267978.4

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97706 AN: 151740 Hom.: 32745 Cov.: 30

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.681

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.773

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.740

Gnomad OTH AF: 0.625

GnomAD4 exome AF: 0.698 AC: 151971 AN: 217852 Hom.: 54399 Cov.: 3 AF XY: 0.691 AC XY: 79772 AN XY: 115366

Gnomad4 AFR exome AF: 0.431

Gnomad4 AMR exome AF: 0.706

Gnomad4 ASJ exome AF: 0.607

Gnomad4 EAS exome AF: 0.526

Gnomad4 SAS exome AF: 0.624

Gnomad4 FIN exome AF: 0.778

Gnomad4 NFE exome AF: 0.744

Gnomad4 OTH exome AF: 0.679

GnomAD4 genome AF: 0.644 AC: 97730 AN: 151860 Hom.: 32743 Cov.: 30 AF XY: 0.643 AC XY: 47691 AN XY: 74202

Gnomad4 AFR AF: 0.459

Gnomad4 AMR AF: 0.681

Gnomad4 ASJ AF: 0.612

Gnomad4 EAS AF: 0.549

Gnomad4 SAS AF: 0.606

Gnomad4 FIN AF: 0.773

Gnomad4 NFE AF: 0.740

Gnomad4 OTH AF: 0.617

Alfa AF: 0.693 Hom.: 4656

Bravo AF: 0.631

Asia WGS AF: 0.575 AC: 2005 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.8
DANN	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs4462560; hg19: chr15-75647964;