rs577726420

Variant names:

• chr16-66437655-G-A
• rs577726420
• NM_001178020.3:c.-22G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-66437655-G-A
• chr16-66437655-G-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_001178020.3(BEAN1):​c.-22G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000318 in 1,535,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00044 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00031 (0 hom.)
• Consequence: BEAN1 NM_001178020.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.678
• 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]

BEAN1 Gene-Disease associations (from GenCC):

• spinocerebellar ataxia type 31

  Inheritance: AD, Unknown Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 16-66437655-G-A is Benign according to our data. Variant chr16-66437655-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2646593.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 67 AD,Unknown gene.

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.-22G>A		5_prime_UTR	Exon 2 of 5	NP_001171491.1	Q3B7T3-1
	BEAN1	NM_001136106.5		c.-303+10224G>A		intron	N/A	NP_001129578.1	Q3B7T3-2
	BEAN1	NM_001197224.4		c.-303+10224G>A		intron	N/A	NP_001184153.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BEAN1	ENST00000536005.7	TSL:1 MANE Select	c.-22G>A		5_prime_UTR	Exon 2 of 5	ENSP00000442793.2	Q3B7T3-1
	BEAN1	ENST00000299694.12	TSL:1	c.-303+10224G>A		intron	N/A	ENSP00000299694.8	Q3B7T3-2
	BEAN1	ENST00000561796.5	TSL:1	n.61+10224G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000440 AC: 67 AN: 152210 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000603

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000365 AC: 49 AN: 134318 AF XY: 0.000342

Gnomad AFR exome AF: 0.000621

Gnomad AMR exome AF: 0.000450

Gnomad ASJ exome AF: 0.000604

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00130

Gnomad NFE exome AF: 0.000399

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000305 AC: 422 AN: 1383500 Hom.: 0 Cov.: 30 AF XY: 0.000300 AC XY: 205 AN XY: 682686

African (AFR) AF: 0.000665 AC: 21 AN: 31590

American (AMR) AF: 0.000364 AC: 13 AN: 35690

Ashkenazi Jewish (ASJ) AF: 0.000795 AC: 20 AN: 25170

East Asian (EAS) AF: 0.00 AC: 0 AN: 35732

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79226

European-Finnish (FIN) AF: 0.00151 AC: 51 AN: 33886

Middle Eastern (MID) AF: 0.000177 AC: 1 AN: 5652

European-Non Finnish (NFE) AF: 0.000272 AC: 293 AN: 1078676

Other (OTH) AF: 0.000380 AC: 22 AN: 57878

GnomAD4 genome AF: 0.000440 AC: 67 AN: 152328 Hom.: 0 Cov.: 32 AF XY: 0.000456 AC XY: 34 AN XY: 74490

African (AFR) AF: 0.000601 AC: 25 AN: 41574

American (AMR) AF: 0.000131 AC: 2 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.000471 AC: 5 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000397 AC: 27 AN: 68022

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000610 Hom.: 0

Bravo AF: 0.000491

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	12
DANN	Benign	0.85
PhyloP100		-0.68
Mutation Taster		=299/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs577726420; hg19: chr16-66471558;