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: 31 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: G2P, Illumina, Ambry Genetics, ClinGen

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).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEIL1	NM_024608.4	MANE Select	c.*589G>A		3_prime_UTR	Exon 10 of 10	NP_078884.2	Q96FI4
	NEIL1	NM_001352520.2		c.*589G>A		3_prime_UTR	Exon 11 of 11	NP_001339449.1
	NEIL1	NR_046311.2		n.2175G>A		non_coding_transcript_exon	Exon 11 of 11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEIL1	ENST00000355059.9	TSL:2 MANE Select	c.*589G>A		3_prime_UTR	Exon 10 of 10	ENSP00000347170.4	Q96FI4
	MAN2C1	ENST00000563660.2	TSL:3	n.178C>T		non_coding_transcript_exon	Exon 1 of 2
	MAN2C1	ENST00000631426.1	TSL:6	n.28C>T		non_coding_transcript_exon	Exon 1 of 1

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 v4.9

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;