rs7069733

Variant names:

• chr10-103538013-C-G
• rs7069733
• NM_004210.5:c.86-32859C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004210.5(NEURL1):​c.86-32859C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 152,040 control chromosomes in the GnomAD database, including 5,612 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 0.24 (5612 hom., cov: 32)
• Consequence: NEURL1 NM_004210.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.610
• Publications: 6 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEURL1	NM_004210.5	c.86-32859C>G		intron_variant	Intron 1 of 5	ENST00000369780.9	NP_004201.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEURL1	ENST00000369780.9	c.86-32859C>G		intron_variant	Intron 1 of 5	1	NM_004210.5	ENSP00000358795.4

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36965 AN: 151920 Hom.: 5604 Cov.: 32

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.0884

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.244 AC: 37027 AN: 152040 Hom.: 5612 Cov.: 32 AF XY: 0.240 AC XY: 17874 AN XY: 74328

African (AFR) AF: 0.423 AC: 17530 AN: 41426

American (AMR) AF: 0.181 AC: 2764 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 1149 AN: 3470

East Asian (EAS) AF: 0.165 AC: 853 AN: 5174

South Asian (SAS) AF: 0.307 AC: 1479 AN: 4810

European-Finnish (FIN) AF: 0.0884 AC: 937 AN: 10602

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11633 AN: 67972

Other (OTH) AF: 0.248 AC: 522 AN: 2104

Alfa AF: 0.106 Hom.: 166

Bravo AF: 0.253

Asia WGS AF: 0.297 AC: 1033 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.9
DANN	Benign	0.69
PhyloP100		0.61
Mutation Taster		=100/0	polymorphism (auto)

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: rs7069733; hg19: chr10-105297770;