Variant 5-172683620-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001142651.3(NEURL1B):c.779C>G(p.Pro260Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000174 in 1,214,098 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000067 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

NEURL1B
NM_001142651.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.67

Variant links:

Genes affected

NEURL1B (HGNC:35422): (neuralized E3 ubiquitin protein ligase 1B) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in ubiquitin-dependent endocytosis. Located in actin cytoskeleton and cytosol. [provided by Alliance of Genome Resources, Apr 2022]

NEURL1B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2150532).

BS2

High AC in GnomAd4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NEURL1B	NM_001142651.3 linkuse as main transcript	c.779C>G	p.Pro260Arg	missense_variant	3/5	ENST00000369800.6	NP_001136123.1
NEURL1B	NM_001308177.2 linkuse as main transcript	c.233C>G	p.Pro78Arg	missense_variant	2/4		NP_001295106.1
NEURL1B	NM_001308178.2 linkuse as main transcript	c.578-2551C>G		intron_variant			NP_001295107.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NEURL1B	ENST00000369800.6 linkuse as main transcript	c.779C>G	p.Pro260Arg	missense_variant	3/5	1	NM_001142651.3	ENSP00000358815.5	A8MQ27-1
NEURL1B	ENST00000522853.5 linkuse as main transcript	c.233C>G	p.Pro78Arg	missense_variant	2/4	1		ENSP00000430001.1	A8MQ27-2
NEURL1B	ENST00000520919.5 linkuse as main transcript	c.578-2551C>G		intron_variant		1		ENSP00000429797.1	A8MQ27-3

Frequencies

GnomAD3 genomes

AF:

0.0000675

AC:

AN:

148164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000244

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000135

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000173

AC:

AN:

5782

Hom.:

AF XY:

0.00

AC XY:

AN XY:

4018

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000347

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000189

AC:

201

AN:

1065934

Hom.:

Cov.:

AF XY:

0.000189

AC XY:

AN XY:

514016

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000918

Gnomad4 NFE exome

AF:

0.000213

Gnomad4 OTH exome

AF:

0.000148

GnomAD4 genome

AF:

0.0000675

AC:

AN:

148164

Hom.:

Cov.:

AF XY:

0.0000554

AC XY:

AN XY:

72232

show subpopulations

Gnomad4 AFR

AF:

0.0000244

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000135

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000831

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 24, 2022

The c.779C>G (p.P260R) alteration is located in exon 3 (coding exon 3) of the NEURL1B gene. This alteration results from a C to G substitution at nucleotide position 779, causing the proline (P) at amino acid position 260 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.0093

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.014

.;T

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.52

T;T

M_CAP

Pathogenic

0.59

MetaRNN

Benign

0.22

T;T

MetaSVM

Benign

-0.57

MutationAssessor

Benign

-0.34

.;N

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.29

Sift

Uncertain

0.0060

D;D

Sift4G

Uncertain

0.012

D;D

Polyphen

0.99

.;D

Vest4

0.20

MutPred

0.29

.;Gain of solvent accessibility (P = 0.0584);

MVP

0.25

MPC

0.54

ClinPred

0.17

GERP RS

3.6

Varity_R

0.19

gMVP

0.68

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over