dbSNP rs4675310: NBEAL1:c.-229-45G>A (chr2-203016111-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_001378026.1(NBEAL1):c.-229-45G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.897 in 289,716 control chromosomes in the GnomAD database, including 116,849 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 0.90 ( 62319 hom., cov: 33)

Exomes 𝑓: 0.89 ( 54530 hom. )

Consequence

NBEAL1
NM_001378026.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.21

Publications

24 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NBEAL1	NM_001378026.1 link	c.-229-45G>A		intron_variant	Intron 1 of 55	ENST00000683969.1	NP_001364955.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NBEAL1	ENST00000683969.1 link	c.-229-45G>A		intron_variant	Intron 1 of 55		NM_001378026.1	ENSP00000508055.1		A0A804HKS6

Frequencies

GnomAD3 genomes

AF:

0.904

AC:

137575

AN:

152190

Hom.:

62269

Cov.:

show subpopulations

Gnomad AFR

AF:

0.944

Gnomad AMI

AF:

0.796

Gnomad AMR

AF:

0.898

Gnomad ASJ

AF:

0.889

Gnomad EAS

AF:

0.985

Gnomad SAS

AF:

0.969

Gnomad FIN

AF:

0.894

Gnomad MID

AF:

0.896

Gnomad NFE

AF:

0.875

Gnomad OTH

AF:

0.867

GnomAD4 exome

AF:

0.890

AC:

122305

AN:

137408

Hom.:

54530

Cov.:

AF XY:

0.890

AC XY:

62764

AN XY:

70534

show subpopulations

African (AFR)

AF:

0.949

AC:

4273

AN:

4504

American (AMR)

AF:

0.899

AC:

4107

AN:

4566

Ashkenazi Jewish (ASJ)

AF:

0.892

AC:

5018

AN:

5626

East Asian (EAS)

AF:

0.991

AC:

11995

AN:

12106

South Asian (SAS)

AF:

0.969

AC:

2012

AN:

2076

European-Finnish (FIN)

AF:

0.889

AC:

6460

AN:

7266

Middle Eastern (MID)

AF:

0.881

AC:

620

AN:

704

European-Non Finnish (NFE)

AF:

0.872

AC:

79532

AN:

91242

Other (OTH)

AF:

0.889

AC:

8288

AN:

9318

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

647

1295

1942

2590

3237

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

258

516

774

1032

1290

<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:

0.904

AC:

137679

AN:

152308

Hom.:

62319

Cov.:

AF XY:

0.907

AC XY:

67579

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.944

AC:

39239

AN:

41568

American (AMR)

AF:

0.898

AC:

13750

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.889

AC:

3085

AN:

3472

East Asian (EAS)

AF:

0.985

AC:

5107

AN:

5184

South Asian (SAS)

AF:

0.968

AC:

4678

AN:

4832

European-Finnish (FIN)

AF:

0.894

AC:

9490

AN:

10610

Middle Eastern (MID)

AF:

0.898

AC:

264

AN:

294

European-Non Finnish (NFE)

AF:

0.875

AC:

59527

AN:

68024

Other (OTH)

AF:

0.860

AC:

1818

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

698

1395

2093

2790

3488

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

904

1808

2712

3616

4520

<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:

0.879

Hom.:

77359

Bravo

AF:

0.904

Asia WGS

AF:

0.958

AC:

3334

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

1.0

(source)

DANN

Benign

0.50

PhyloP100

-1.2

PromoterAI

0.011

Neutral

(source)

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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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