15-75355623-G-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 30 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]

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]

MAN2C1 Gene-Disease associations (from GenCC):

• congenital disorder of deglycosylation 2

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Illumina, G2P

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024608.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEIL1	NM_024608.4	MANE Select	c.*589G>C		3_prime_UTR	Exon 10 of 10	NP_078884.2
	NEIL1	NM_001352520.2		c.*589G>C		3_prime_UTR	Exon 11 of 11	NP_001339449.1
	NEIL1	NR_046311.2		n.2175G>C		non_coding_transcript_exon	Exon 11 of 11

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEIL1	ENST00000355059.9	TSL:2 MANE Select	c.*589G>C		3_prime_UTR	Exon 10 of 10	ENSP00000347170.4
	MAN2C1	ENST00000563660.2	TSL:3	n.178C>G		non_coding_transcript_exon	Exon 1 of 2
	MAN2C1	ENST00000631426.1	TSL:6	n.28C>G		non_coding_transcript_exon	Exon 1 of 1

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

African (AFR) AF: 0.431 AC: 2749 AN: 6380

American (AMR) AF: 0.706 AC: 5554 AN: 7872

Ashkenazi Jewish (ASJ) AF: 0.607 AC: 4033 AN: 6640

East Asian (EAS) AF: 0.526 AC: 6560 AN: 12480

South Asian (SAS) AF: 0.624 AC: 18068 AN: 28968

European-Finnish (FIN) AF: 0.778 AC: 7890 AN: 10144

Middle Eastern (MID) AF: 0.543 AC: 516 AN: 950

European-Non Finnish (NFE) AF: 0.744 AC: 98343 AN: 132258

Other (OTH) AF: 0.679 AC: 8258 AN: 12160

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

African (AFR) AF: 0.459 AC: 19007 AN: 41384

American (AMR) AF: 0.681 AC: 10397 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.612 AC: 2122 AN: 3466

East Asian (EAS) AF: 0.549 AC: 2799 AN: 5102

South Asian (SAS) AF: 0.606 AC: 2920 AN: 4816

European-Finnish (FIN) AF: 0.773 AC: 8172 AN: 10570

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.740 AC: 50258 AN: 67942

Other (OTH) AF: 0.617 AC: 1299 AN: 2104

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.8
DANN	Benign	0.49
PhyloP100		0.83

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

Other links and lift over

dbSNP: rs4462560; hg19: chr15-75647964;