Genetic Variant NM_001378026.1:c.502C>T (chr2-203057440-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001378026.1(NBEAL1):c.502C>T(p.His168Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000839 in 1,549,702 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 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000079 ( 0 hom. )

Consequence

NBEAL1
NM_001378026.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.25

Publications

0 publications found

Variant links:

Genes affected

NBEAL1 (HGNC:20681): (neurobeachin like 1) Predicted to enable protein kinase binding activity. Predicted to be involved in protein localization. Predicted to be active in cytosol and membrane. [provided by Alliance of Genome Resources, Apr 2022]

NBEAL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29344794).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378026.1. 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
	NBEAL1	NM_001378026.1	MANE Select	c.502C>T	p.His168Tyr	missense	Exon 6 of 56	NP_001364955.1	A0A804HKS6
	NBEAL1	NM_001114132.2		c.502C>T	p.His168Tyr	missense	Exon 6 of 55	NP_001107604.1	Q6ZS30-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NBEAL1	ENST00000683969.1	MANE Select	c.502C>T	p.His168Tyr	missense	Exon 6 of 56	ENSP00000508055.1	A0A804HKS6
NBEAL1	ENST00000478884.5	TSL:1	n.789C>T		non_coding_transcript_exon	Exon 6 of 7
NBEAL1	ENST00000449802.5	TSL:5	c.502C>T	p.His168Tyr	missense	Exon 6 of 55	ENSP00000399903.1	Q6ZS30-2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152188

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:

0.000192

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000639

AC:

AN:

156502

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000787

AC:

AN:

1397396

Hom.:

Cov.:

AF XY:

0.0000116

AC XY:

AN XY:

689362

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31722

American (AMR)

AF:

0.00

AC:

AN:

35464

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25102

East Asian (EAS)

AF:

0.00

AC:

AN:

36026

South Asian (SAS)

AF:

0.0000886

AC:

AN:

79042

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49236

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5684

European-Non Finnish (NFE)

AF:

9.28e-7

AC:

AN:

1077216

Other (OTH)

AF:

0.0000518

AC:

AN:

57904

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

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:

0.0000131

AC:

AN:

152306

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41576

American (AMR)

AF:

0.00

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5188

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.00

Hom.:

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

0.095

BayesDel_addAF

Benign

-0.087

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0059

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.025

MetaRNN

Benign

0.29

MetaSVM

Benign

-0.47

MutationAssessor

Benign

1.7

PhyloP100

7.3

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-2.2

REVEL

Benign

0.17

Sift

Uncertain

0.014

Sift4G

Uncertain

0.020

Polyphen

0.13

Vest4

0.38

MutPred

0.32

Gain of helix (P = 0.062)

MVP

0.62

MPC

0.19

ClinPred

0.60

GERP RS

5.6

PromoterAI

-0.021

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.21

gMVP

0.43

Mutation Taster

=69/31

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