10-103553282-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004210.5(NEURL1):c.86-17590A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.868 in 152,196 control chromosomes in the GnomAD database, including 57,711 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 0.87 (57711 hom., cov: 33)
• Consequence: NEURL1 NM_004210.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.641

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEURL1	NM_004210.5	c.86-17590A>G		intron_variant		ENST00000369780.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEURL1	ENST00000369780.9	c.86-17590A>G		intron_variant		1	NM_004210.5	P1

Frequencies

GnomAD3 genomes AF: 0.868 AC: 131931 AN: 152076 Hom.: 57646 Cov.: 33

Gnomad AFR AF: 0.966

Gnomad AMI AF: 0.599

Gnomad AMR AF: 0.880

Gnomad ASJ AF: 0.864

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.895

Gnomad FIN AF: 0.778

Gnomad MID AF: 0.885

Gnomad NFE AF: 0.810

Gnomad OTH AF: 0.873

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.868 AC: 132056 AN: 152196 Hom.: 57711 Cov.: 33 AF XY: 0.867 AC XY: 64529 AN XY: 74400

Gnomad4 AFR AF: 0.966

Gnomad4 AMR AF: 0.881

Gnomad4 ASJ AF: 0.864

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.895

Gnomad4 FIN AF: 0.778

Gnomad4 NFE AF: 0.810

Gnomad4 OTH AF: 0.874

Alfa AF: 0.826 Hom.: 49309

Bravo AF: 0.881

Asia WGS AF: 0.956 AC: 3322 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.4
Dann	Benign	0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs912889; hg19: chr10-105313039;