Variant chr16-66469802-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001178020.3(BEAN1):c.226C>A(p.Arg76Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0101 in 1,535,802 control chromosomes in the GnomAD database, including 109 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0081 ( 9 hom., cov: 32)

Exomes 𝑓: 0.010 ( 100 hom. )

Consequence

BEAN1
NM_001178020.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.76

Variant links:

Genes affected

BEAN1 (HGNC:24160): (brain expressed associated with NEDD4 1) The protein encoded by this gene is one of several proteins that interact with NEDD4, a member of a family of ubiquitin-protein ligases. These proteins have PY motifs in common that bind to the WW domains of NEDD4. NEDD4 is developmentally regulated, and is highly expressed in embryonic tissues. Mutations in this gene (i.e., intronic insertions of >100 copies of pentanucleotide repeats including a (TGGAA)n sequence) are associated with spinocerebellar ataxia type 31. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2010]

BEAN1 links:

LOC124903698 (HGNC:):

LOC124903698 links:

BEAN1-AS1 (HGNC:51114): (BEAN1 antisense RNA 1)

BEAN1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034638345).

BP6

Variant 16-66469802-C-A is Benign according to our data. Variant chr16-66469802-C-A is described in ClinVar as [Benign]. Clinvar id is 2646598.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-66469802-C-A is described in Lovd as [Benign].

BS2

High AC in GnomAd4 at 1231 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BEAN1	NM_001178020.3 link	c.226C>A	p.Arg76Ser	missense_variant	Exon 3 of 5	ENST00000536005.7	NP_001171491.1	Q3B7T3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BEAN1	ENST00000536005.7 link	c.226C>A	p.Arg76Ser	missense_variant	Exon 3 of 5	1	NM_001178020.3	ENSP00000442793.2		Q3B7T3-1
ENSG00000260851	ENST00000561728.1 link	n.*523G>T		downstream_gene_variant		2		ENSP00000462196.1		J3KRW8

Frequencies

GnomAD3 genomes

AF:

0.00809

AC:

1230

AN:

152002

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00159

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.00301

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00853

Gnomad FIN

AF:

0.0261

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0113

Gnomad OTH

AF:

0.00576

GnomAD3 exomes

AF:

0.00775

AC:

1068

AN:

137830

Hom.:

AF XY:

0.00835

AC XY:

624

AN XY:

74744

show subpopulations

Gnomad AFR exome

AF:

0.00170

Gnomad AMR exome

AF:

0.00351

Gnomad ASJ exome

AF:

0.000963

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00752

Gnomad FIN exome

AF:

0.0239

Gnomad NFE exome

AF:

0.0113

Gnomad OTH exome

AF:

0.00740

GnomAD4 exome

AF:

0.0103

AC:

14219

AN:

1383682

Hom.:

100

Cov.:

AF XY:

0.0102

AC XY:

6956

AN XY:

682786

show subpopulations

Gnomad4 AFR exome

AF:

0.00123

Gnomad4 AMR exome

AF:

0.00353

Gnomad4 ASJ exome

AF:

0.00119

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00785

Gnomad4 FIN exome

AF:

0.0229

Gnomad4 NFE exome

AF:

0.0113

Gnomad4 OTH exome

AF:

0.00760

GnomAD4 genome

AF:

0.00809

AC:

1231

AN:

152120

Hom.:

Cov.:

AF XY:

0.00910

AC XY:

677

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.00159

Gnomad4 AMR

AF:

0.00301

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00874

Gnomad4 FIN

AF:

0.0261

Gnomad4 NFE

AF:

0.0113

Gnomad4 OTH

AF:

0.00570

Alfa

AF:

0.00398

Hom.:

Bravo

AF:

0.00603

TwinsUK

AF:

0.00593

AC:

ALSPAC

AF:

0.0106

AC:

ExAC

AF:

0.00444

AC:

259

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2024

BEAN1: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.024

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.50

MetaRNN

Benign

0.0035

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.4

REVEL

Benign

0.063

Sift

Benign

0.11

Sift4G

Benign

0.31

Vest4

0.38

MVP

0.099

ClinPred

0.016

GERP RS

4.1

Varity_R

0.17

gMVP

0.23

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over