16-66480611-G-A

Variant names:

• chr16-66480611-G-A
• rs746865919
• NM_001178020.3:c.466G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001178020.3(BEAN1):​c.466G>A​(p.Ala156Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: BEAN1 NM_001178020.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.09

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]

ENSG00000260851 (HGNC:):

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

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BEAN1	NM_001178020.3	c.466G>A	p.Ala156Thr	missense_variant	Exon 5 of 5	ENST00000536005.7	NP_001171491.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BEAN1	ENST00000536005.7	c.466G>A	p.Ala156Thr	missense_variant	Exon 5 of 5	1	NM_001178020.3	ENSP00000442793.2
ENSG00000260851	ENST00000561728.1	n.*11+553C>T		intron_variant	Intron 3 of 5	2		ENSP00000462196.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Uncertain	0.091	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.20	T;.
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.46	T;T
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Uncertain	2.0	M;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.6	D;D
REVEL	Benign	0.15
Sift	Uncertain	0.0050	D;D
Sift4G	Benign	0.30	T;D
Polyphen		1.0	D;.
Vest4		0.65
MutPred		0.23		Gain of glycosylation at A156 (P = 0.0158);.;
MVP		0.15
ClinPred		0.96	D
GERP RS		3.7
Varity_R		0.19
gMVP		0.17

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

Other links and lift over

dbSNP: rs746865919; hg19: chr16-66514514;