Genetic Variant NEURL1B:c.1298-100G>A (chr5-172686071-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001142651.3(NEURL1B):c.1298-100G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,418,122 control chromosomes in the GnomAD database, including 11,612 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 0.17 ( 3016 hom., cov: 32)

Exomes 𝑓: 0.11 ( 8596 hom. )

Consequence

NEURL1B
NM_001142651.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.47

Publications

4 publications found

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:

ENSG00000253445 (HGNC:):

ENSG00000253445 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
NEURL1B	NM_001142651.3 link	c.1298-100G>A	intron_variant	Intron 3 of 4	ENST00000369800.6	NP_001136123.1
NEURL1B	NM_001308177.2 link	c.752-100G>A	intron_variant	Intron 2 of 3		NP_001295106.1
NEURL1B	NM_001308178.2 link	c.578-100G>A	intron_variant	Intron 2 of 3		NP_001295107.1
LOC107986479	XR_001742997.1 link	n.*234C>T	downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEURL1B	ENST00000369800.6 link	c.1298-100G>A		intron_variant	Intron 3 of 4	1	NM_001142651.3	ENSP00000358815.5		A8MQ27-1

Frequencies

GnomAD3 genomes

AF:

0.175

AC:

26542

AN:

152030

Hom.:

2999

Cov.:

show subpopulations

Gnomad AFR

AF:

0.320

Gnomad AMI

AF:

0.112

Gnomad AMR

AF:

0.194

Gnomad ASJ

AF:

0.0620

Gnomad EAS

AF:

0.179

Gnomad SAS

AF:

0.100

Gnomad FIN

AF:

0.139

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.0999

Gnomad OTH

AF:

0.153

GnomAD4 exome

AF:

0.107

AC:

135607

AN:

1265974

Hom.:

8596

AF XY:

0.106

AC XY:

65951

AN XY:

622170

show subpopulations

African (AFR)

AF:

0.327

AC:

9369

AN:

28668

American (AMR)

AF:

0.222

AC:

6640

AN:

29932

Ashkenazi Jewish (ASJ)

AF:

0.0605

AC:

1251

AN:

20692

East Asian (EAS)

AF:

0.134

AC:

4691

AN:

34942

South Asian (SAS)

AF:

0.0972

AC:

6567

AN:

67590

European-Finnish (FIN)

AF:

0.132

AC:

5623

AN:

42680

Middle Eastern (MID)

AF:

0.0778

AC:

387

AN:

4974

European-Non Finnish (NFE)

AF:

0.0965

AC:

94913

AN:

983514

Other (OTH)

AF:

0.116

AC:

6166

AN:

52982

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

5660

11320

16981

22641

28301

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.175

AC:

26608

AN:

152148

Hom.:

3016

Cov.:

AF XY:

0.176

AC XY:

13108

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.321

AC:

13298

AN:

41482

American (AMR)

AF:

0.194

AC:

2963

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0620

AC:

215

AN:

3470

East Asian (EAS)

AF:

0.179

AC:

925

AN:

5172

South Asian (SAS)

AF:

0.0994

AC:

479

AN:

4820

European-Finnish (FIN)

AF:

0.139

AC:

1476

AN:

10596

Middle Eastern (MID)

AF:

0.105

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.100

AC:

6797

AN:

68002

Other (OTH)

AF:

0.152

AC:

322

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1054

2109

3163

4218

5272

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0982

Hom.:

478

Bravo

AF:

0.189

Asia WGS

AF:

0.145

AC:

504

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.011

(source)

DANN

Benign

0.47

PhyloP100

-2.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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5-172686071-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over