rs902991

Positions:

• chr10-103583143-C-T

Variant summary

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

The NM_004210.5(NEURL1):​c.650-1393C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.771 in 152,058 control chromosomes in the GnomAD database, including 45,797 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 0.77 (45797 hom., cov: 31)
• Consequence: NEURL1 NM_004210.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.503

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]

(HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEURL1	NM_004210.5	c.650-1393C>T		intron_variant		ENST00000369780.9	NP_004201.3
LOC124902496	XR_007062277.1	n.601G>A		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEURL1	ENST00000369780.9	c.650-1393C>T		intron_variant		1	NM_004210.5	ENSP00000358795	P1
	ENST00000663302.1	n.545G>A		non_coding_transcript_exon_variant	1/3

Frequencies

GnomAD3 genomes AF: 0.771 AC: 117198 AN: 151940 Hom.: 45743 Cov.: 31

Gnomad AFR AF: 0.880

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.798

Gnomad ASJ AF: 0.776

Gnomad EAS AF: 0.795

Gnomad SAS AF: 0.855

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.718

Gnomad OTH AF: 0.780

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

GnomAD4 genome AF: 0.771 AC: 117310 AN: 152058 Hom.: 45797 Cov.: 31 AF XY: 0.770 AC XY: 57193 AN XY: 74308

Gnomad4 AFR AF: 0.880

Gnomad4 AMR AF: 0.799

Gnomad4 ASJ AF: 0.776

Gnomad4 EAS AF: 0.795

Gnomad4 SAS AF: 0.854

Gnomad4 FIN AF: 0.620

Gnomad4 NFE AF: 0.718

Gnomad4 OTH AF: 0.782

Alfa AF: 0.739 Hom.: 67853

Bravo AF: 0.788

Asia WGS AF: 0.845 AC: 2939 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	9.0
DANN	Benign	0.57

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: rs902991; hg19: chr10-105342900;