10-103562616-C-T

Variant names:

• chr10-103562616-C-T
• rs11191727
• NM_004210.5:c.86-8256C>T

Variant summary

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

The NM_004210.5(NEURL1):​c.86-8256C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,106 control chromosomes in the GnomAD database, including 1,500 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 0.14 (1500 hom., cov: 32)
• Consequence: NEURL1 NM_004210.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00900
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004210.5. 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.86-8256C>T		intron	N/A	NP_004201.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEURL1	ENST00000369780.9	TSL:1 MANE Select	c.86-8256C>T		intron	N/A	ENSP00000358795.4	O76050-1
	NEURL1	ENST00000945279.1		c.86-21920C>T		intron	N/A	ENSP00000615338.1
	NEURL1	ENST00000437579.1	TSL:2	c.34+7203C>T		intron	N/A	ENSP00000416709.1	X6RLA8

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20646 AN: 151988 Hom.: 1502 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.0920

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.136 AC: 20657 AN: 152106 Hom.: 1500 Cov.: 32 AF XY: 0.135 AC XY: 10002 AN XY: 74330

African (AFR) AF: 0.112 AC: 4667 AN: 41494

American (AMR) AF: 0.116 AC: 1775 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 736 AN: 3462

East Asian (EAS) AF: 0.163 AC: 844 AN: 5182

South Asian (SAS) AF: 0.222 AC: 1065 AN: 4804

European-Finnish (FIN) AF: 0.0920 AC: 972 AN: 10570

Middle Eastern (MID) AF: 0.175 AC: 51 AN: 292

European-Non Finnish (NFE) AF: 0.149 AC: 10118 AN: 68002

Other (OTH) AF: 0.163 AC: 343 AN: 2110

Alfa AF: 0.142 Hom.: 3226

Bravo AF: 0.133

Asia WGS AF: 0.217 AC: 754 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.6
DANN	Benign	0.61
PhyloP100		0.0090
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: rs11191727; hg19: chr10-105322373;