Genetic Variant NM_004210.5:c.637G>A (chr10-103571810-G-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_004210.5(NEURL1):c.637G>A(p.Val213Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000406 in 1,602,794 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 0.000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

NEURL1
NM_004210.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.13

Publications

0 publications found

Variant links:

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]

NEURL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.30067143).

BS2

High AC in GnomAd4 at 10 AD gene.

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.637G>A	p.Val213Ile	missense	Exon 3 of 6	NP_004201.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NEURL1	ENST00000369780.9	TSL:1 MANE Select	c.637G>A	p.Val213Ile	missense	Exon 3 of 6	ENSP00000358795.4	O76050-1
NEURL1	ENST00000437579.1	TSL:2	c.586G>A	p.Val196Ile	missense	Exon 3 of 3	ENSP00000416709.1	X6RLA8
NEURL1	ENST00000945279.1		c.86-12726G>A		intron	N/A	ENSP00000615338.1

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000210

AC:

AN:

238144

AF XY:

0.0000233

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000467

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000379

AC:

AN:

1450468

Hom.:

Cov.:

AF XY:

0.0000458

AC XY:

AN XY:

720450

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33368

American (AMR)

AF:

0.00

AC:

AN:

44300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25470

East Asian (EAS)

AF:

0.00

AC:

AN:

39610

South Asian (SAS)

AF:

0.0000118

AC:

AN:

84596

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50944

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5718

European-Non Finnish (NFE)

AF:

0.0000452

AC:

AN:

1106444

Other (OTH)

AF:

0.0000666

AC:

AN:

60018

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000656

AC:

AN:

152326

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41570

American (AMR)

AF:

0.00

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

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:

0.0000868

Hom.:

Bravo

AF:

0.0000642

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000247

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.42

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.077

Eigen

Pathogenic

0.68

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.0062

MetaRNN

Benign

0.30

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.90

PhyloP100

8.1

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.38

REVEL

Benign

0.21

Sift

Benign

0.12

Sift4G

Benign

0.19

Polyphen

1.0

Vest4

0.47

MVP

0.43

MPC

0.99

ClinPred

0.62

GERP RS

5.6

Varity_R

0.15

gMVP

0.42

Mutation Taster

=93/7

polymorphism

(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

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