rs1963394475

Variant names:

• chr16-66469703-A-G
• rs1963394475
• NM_001178020.3:c.127A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001178020.3(BEAN1):​c.127A>G​(p.Ile43Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000723 in 1,383,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I43T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: BEAN1 NM_001178020.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.86
• Publications: 0 publications found

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]

LOC124903698 (HGNC:):

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18872726).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001178020.3. 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
	BEAN1	NM_001178020.3	MANE Select	c.127A>G	p.Ile43Val	missense	Exon 3 of 5	NP_001171491.1	Q3B7T3-1
	BEAN1	NM_001136106.5		c.-201A>G		5_prime_UTR	Exon 2 of 4	NP_001129578.1	Q3B7T3-2
	BEAN1	NM_001197224.4		c.-201A>G		5_prime_UTR	Exon 2 of 5	NP_001184153.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BEAN1	ENST00000536005.7	TSL:1 MANE Select	c.127A>G	p.Ile43Val	missense	Exon 3 of 5	ENSP00000442793.2	Q3B7T3-1
	BEAN1	ENST00000299694.12	TSL:1	c.-201A>G		5_prime_UTR	Exon 2 of 4	ENSP00000299694.8	Q3B7T3-2
	BEAN1	ENST00000561796.5	TSL:1	n.163A>G		non_coding_transcript_exon	Exon 2 of 5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.23e-7 AC: 1 AN: 1383850 Hom.: 0 Cov.: 32 AF XY: 0.00000146 AC XY: 1 AN XY: 682864

African (AFR) AF: 0.00 AC: 0 AN: 31594

American (AMR) AF: 0.0000280 AC: 1 AN: 35700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35734

South Asian (SAS) AF: 0.00 AC: 0 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33908

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078890

Other (OTH) AF: 0.00 AC: 0 AN: 57910

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Benign	0.083
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
PhyloP100		2.9
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.70	N
REVEL	Benign	0.077
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.053	T
Vest4		0.31
MutPred		0.28		Loss of sheet (P = 0.1398)
MVP		0.072
ClinPred		0.70	D
GERP RS		4.1
PromoterAI		-0.058	Neutral
Varity_R		0.31
gMVP		0.49

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

Other links and lift over

dbSNP: rs1963394475; hg19: chr16-66503606;