10-103562616-C-T

Position:

• chr10-103562616-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.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

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 (SAS) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEURL1	NM_004210.5	c.86-8256C>T		intron_variant		ENST00000369780.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEURL1	ENST00000369780.9	c.86-8256C>T		intron_variant		1	NM_004210.5	P1
NEURL1	ENST00000437579.1	c.34+7203C>T		intron_variant		2
NEURL1	ENST00000455386.1	c.-141+4368C>T		intron_variant		2

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

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.0920

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.163

Alfa AF: 0.143 Hom.: 2206

Bravo AF: 0.133

Asia WGS AF: 0.217 AC: 754 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	4.6
DANN	Benign	0.61

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: rs11191727; hg19: chr10-105322373;