Genetic Variant NM_001178020.3:c.289+10C>T (chr16-66469875-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001178020.3(BEAN1):c.289+10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0221 in 1,531,706 control chromosomes in the GnomAD database, including 598 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.020 ( 50 hom., cov: 31)

Exomes 𝑓: 0.022 ( 548 hom. )

Consequence

BEAN1
NM_001178020.3 intron

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -4.45

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:

ENSG00000260851 (HGNC:):

ENSG00000260851 links:

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

BEAN1-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 16-66469875-C-T is Benign according to our data. Variant chr16-66469875-C-T is described in ClinVar as [Benign]. Clinvar id is 3041320.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-66469875-C-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BEAN1	NM_001178020.3 link	c.289+10C>T		intron_variant	Intron 3 of 4	ENST00000536005.7	NP_001171491.1	Q3B7T3-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
BEAN1	ENST00000536005.7 link	c.289+10C>T	intron_variant	Intron 3 of 4	1	NM_001178020.3	ENSP00000442793.2	Q3B7T3-1
ENSG00000260851	ENST00000561728.1 link	n.*450G>A	non_coding_transcript_exon_variant	Exon 6 of 6	2		ENSP00000462196.1	J3KRW8
ENSG00000260851	ENST00000561728.1 link	n.*450G>A	3_prime_UTR_variant	Exon 6 of 6	2		ENSP00000462196.1	J3KRW8

Frequencies

GnomAD3 genomes

AF:

0.0201

AC:

3054

AN:

151934

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0242

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0110

Gnomad ASJ

AF:

0.0159

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0660

Gnomad FIN

AF:

0.0118

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0197

Gnomad OTH

AF:

0.0173

GnomAD3 exomes

AF:

0.0248

AC:

3317

AN:

133650

Hom.:

AF XY:

0.0279

AC XY:

2022

AN XY:

72512

show subpopulations

Gnomad AFR exome

AF:

0.0229

Gnomad AMR exome

AF:

0.00735

Gnomad ASJ exome

AF:

0.0173

Gnomad EAS exome

AF:

0.0000952

Gnomad SAS exome

AF:

0.0684

Gnomad FIN exome

AF:

0.0123

Gnomad NFE exome

AF:

0.0223

Gnomad OTH exome

AF:

0.0220

GnomAD4 exome

AF:

0.0223

AC:

30805

AN:

1379654

Hom.:

548

Cov.:

AF XY:

0.0238

AC XY:

16172

AN XY:

680390

show subpopulations

Gnomad4 AFR exome

AF:

0.0230

Gnomad4 AMR exome

AF:

0.00844

Gnomad4 ASJ exome

AF:

0.0185

Gnomad4 EAS exome

AF:

0.000140

Gnomad4 SAS exome

AF:

0.0661

Gnomad4 FIN exome

AF:

0.0104

Gnomad4 NFE exome

AF:

0.0208

Gnomad4 OTH exome

AF:

0.0224

GnomAD4 genome

AF:

0.0201

AC:

3057

AN:

152052

Hom.:

Cov.:

AF XY:

0.0200

AC XY:

1486

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.0241

Gnomad4 AMR

AF:

0.0109

Gnomad4 ASJ

AF:

0.0159

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.0661

Gnomad4 FIN

AF:

0.0118

Gnomad4 NFE

AF:

0.0197

Gnomad4 OTH

AF:

0.0176

Alfa

AF:

0.0187

Hom.:

Bravo

AF:

0.0190

Asia WGS

AF:

0.0380

AC:

134

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

BEAN1-related disorder

Benign:1

Sep 10, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.088

DANN

Benign

0.87

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