5-172686071-G-C

Variant names:

• chr5-172686071-G-C
• rs17075071
• NM_001142651.3:c.1298-100G>C

Variant summary

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

The NM_001142651.3(NEURL1B):​c.1298-100G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000789 in 1,267,026 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 7.9e-7 (0 hom.)
• Consequence: NEURL1B NM_001142651.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.47
• Publications: 4 publications found

Genes affected

NEURL1B (HGNC:35422): (neuralized E3 ubiquitin protein ligase 1B) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in ubiquitin-dependent endocytosis. Located in actin cytoskeleton and cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000253445 (HGNC:):

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=-0.97).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEURL1B	NM_001142651.3	c.1298-100G>C		intron_variant	Intron 3 of 4	ENST00000369800.6	NP_001136123.1
NEURL1B	NM_001308177.2	c.752-100G>C		intron_variant	Intron 2 of 3		NP_001295106.1
NEURL1B	NM_001308178.2	c.578-100G>C		intron_variant	Intron 2 of 3		NP_001295107.1
LOC107986479	XR_001742997.1	n.*234C>G		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEURL1B	ENST00000369800.6	c.1298-100G>C		intron_variant	Intron 3 of 4	1	NM_001142651.3	ENSP00000358815.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.89e-7 AC: 1 AN: 1267026 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 622666

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 28720

American (AMR) AF: 0.00 AC: 0 AN: 29974

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20702

East Asian (EAS) AF: 0.0000286 AC: 1 AN: 34954

South Asian (SAS) AF: 0.00 AC: 0 AN: 67618

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42708

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4976

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 984344

Other (OTH) AF: 0.00 AC: 0 AN: 53030

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.0050
DANN	Benign	0.36
PhyloP100		-2.5

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: rs17075071; hg19: chr5-172113074;