rs4462560

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr15-75355623-G-A
• chr15-75355623-G-C
• chr15-75355623-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024608.4(NEIL1):​c.*589G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEIL1	NM_024608.4	c.*589G>A		3_prime_UTR_variant	Exon 10 of 10	ENST00000355059.9	NP_078884.2
MAN2C1	NM_006715.4	c.*283C>T		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>A		3_prime_UTR_variant	Exon 10 of 10	2	NM_024608.4	ENSP00000347170.4
MAN2C1	ENST00000267978.10	c.*283C>T		downstream_gene_variant		1	NM_006715.4	ENSP00000267978.4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 218504 Hom.: 0 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 115728

African (AFR) AF: 0.00 AC: 0 AN: 6412

American (AMR) AF: 0.00 AC: 0 AN: 7888

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6672

East Asian (EAS) AF: 0.00 AC: 0 AN: 12522

South Asian (SAS) AF: 0.00 AC: 0 AN: 29050

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10170

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 954

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 132630

Other (OTH) AF: 0.00 AC: 0 AN: 12206

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.1
DANN	Benign	0.46
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;