ENST00000453753.5:n.*97A>G

Variant names:

• chr10-103494708-T-C
• NM_004210.5:c.85+236T>C

Variant summary

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

The ENST00000453753.5(NEURL1-AS1):​n.98A>G variant causes a non coding transcript exon 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: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NEURL1-AS1 ENST00000453753.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.545
• Publications: 0 publications found

Genes affected

NEURL1 (HGNC:7761): (neuralized E3 ubiquitin protein ligase 1) Predicted to enable translation factor activity, non-nucleic acid binding and ubiquitin protein ligase activity. Involved in negative regulation of Notch signaling pathway; negative regulation of cell population proliferation; and positive regulation of apoptotic process. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

NEURL1-AS1 (HGNC:51220): (NEURL1 antisense RNA 1)

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=-0.52).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000453753.5. 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
	NEURL1	NM_004210.5	MANE Select	c.85+236T>C		intron	N/A	NP_004201.3
	NEURL1-AS1	NR_120675.1		n.147A>G		non_coding_transcript_exon	Exon 3 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEURL1	ENST00000369780.9	TSL:1 MANE Select	c.85+236T>C		intron	N/A	ENSP00000358795.4	O76050-1
	NEURL1	ENST00000945279.1		c.85+236T>C		intron	N/A	ENSP00000615338.1
	NEURL1-AS1	ENST00000453753.5	TSL:5	n.98A>G		non_coding_transcript_exon	Exon 3 of 4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 374694 Hom.: 0 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 197468

African (AFR) AF: 0.00 AC: 0 AN: 7804

American (AMR) AF: 0.00 AC: 0 AN: 11366

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11732

East Asian (EAS) AF: 0.00 AC: 0 AN: 23242

South Asian (SAS) AF: 0.00 AC: 0 AN: 36762

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27572

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1750

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 232040

Other (OTH) AF: 0.00 AC: 0 AN: 22426

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	17
DANN	Benign	0.64
PhyloP100		0.55

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr10-105254465;