Genetic Variant NEURL4:p.Ala1527Thr (chr17-7316233-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_032442.3(NEURL4):c.4579G>A(p.Ala1527Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000656 in 1,613,772 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00091 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00063 ( 3 hom. )

Consequence

NEURL4
NM_032442.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.705

Publications

2 publications found

Variant links:

Genes affected

NEURL4 (HGNC:34410): (neuralized E3 ubiquitin protein ligase 4) The protein encoded by this gene is predicted and it includes two isoforms resulting from two alternatively spliced transcript variants. [provided by RefSeq, Jul 2008]

NEURL4 links:

ENSG00000261915 (HGNC:):

ENSG00000261915 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034599602).

BP6

Variant 17-7316233-C-T is Benign according to our data. Variant chr17-7316233-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3390331.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032442.3. 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
	NEURL4	NM_032442.3	MANE Select	c.4579G>A	p.Ala1527Thr	missense	Exon 29 of 29	NP_115818.2	Q96JN8-1
	NEURL4	NM_001005408.2		c.4573G>A	p.Ala1525Thr	missense	Exon 29 of 29	NP_001005408.1	Q96JN8-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NEURL4	ENST00000399464.7	TSL:1 MANE Select	c.4579G>A	p.Ala1527Thr	missense	Exon 29 of 29	ENSP00000382390.2	Q96JN8-1
NEURL4	ENST00000315614.11	TSL:1	c.4573G>A	p.Ala1525Thr	missense	Exon 29 of 29	ENSP00000319826.7	Q96JN8-2
ENSG00000261915	ENST00000575474.1	TSL:5	n.975+43G>A		intron	N/A	ENSP00000468772.1	K7ESM1

Frequencies

GnomAD3 genomes

AF:

0.000914

AC:

139

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00971

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.00114

AC:

284

AN:

249484

AF XY:

0.00116

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00951

Gnomad NFE exome

AF:

0.000512

Gnomad OTH exome

AF:

0.000825

GnomAD4 exome

AF:

0.000629

AC:

919

AN:

1461516

Hom.:

Cov.:

AF XY:

0.000612

AC XY:

445

AN XY:

727050

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.0000447

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000727

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000104

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.00871

AC:

465

AN:

53414

Middle Eastern (MID)

AF:

0.000882

AC:

AN:

5670

European-Non Finnish (NFE)

AF:

0.000347

AC:

386

AN:

1111786

Other (OTH)

AF:

0.000547

AC:

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

116

173

231

289

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000913

AC:

139

AN:

152256

Hom.:

Cov.:

AF XY:

0.00138

AC XY:

103

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41540

American (AMR)

AF:

0.00

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.000577

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00971

AC:

103

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000456

AC:

AN:

68006

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000475

Hom.:

Bravo

AF:

0.000185

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000481

AC:

ExAC

AF:

0.000976

AC:

118

EpiCase

AF:

0.000763

EpiControl

AF:

0.000474

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0085

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.067

LIST_S2

Benign

0.75

M_CAP

Benign

0.0076

MetaRNN

Benign

0.0035

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.89

PhyloP100

0.70

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.90

REVEL

Benign

0.036

Sift

Benign

0.21

Sift4G

Benign

0.30

Polyphen

0.0070

Vest4

0.042

MVP

0.043

MPC

0.51

ClinPred

0.023

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.082

gMVP

0.23

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over