chr16-66437945-G-A

Variant names:

• chr16-66437945-G-A
• rs149138473
• NM_001178020.3:c.25+244G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001178020.3(BEAN1):​c.25+244G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00232 in 606,176 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0025 (3 hom.)
• Consequence: BEAN1 NM_001178020.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.01
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 16-66437945-G-A is Benign according to our data. Variant chr16-66437945-G-A is described in ClinVar as Benign. ClinVar VariationId is 2646594.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 283 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.25+244G>A		intron	N/A	NP_001171491.1	Q3B7T3-1
	BEAN1	NM_001136106.5		c.-303+10514G>A		intron	N/A	NP_001129578.1	Q3B7T3-2
	BEAN1	NM_001197224.4		c.-303+10514G>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.25+244G>A		intron	N/A	ENSP00000442793.2	Q3B7T3-1
	BEAN1	ENST00000299694.12	TSL:1	c.-303+10514G>A		intron	N/A	ENSP00000299694.8	Q3B7T3-2
	BEAN1	ENST00000561796.5	TSL:1	n.61+10514G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00187 AC: 282 AN: 150980 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000586

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000724

Gnomad ASJ AF: 0.00522

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00333

Gnomad OTH AF: 0.00194

GnomAD4 exome AF: 0.00247 AC: 1125 AN: 455076 Hom.: 3 Cov.: 3 AF XY: 0.00232 AC XY: 557 AN XY: 239774

African (AFR) AF: 0.000685 AC: 9 AN: 13146

American (AMR) AF: 0.000807 AC: 19 AN: 23542

Ashkenazi Jewish (ASJ) AF: 0.00657 AC: 94 AN: 14306

East Asian (EAS) AF: 0.00 AC: 0 AN: 30246

South Asian (SAS) AF: 0.000148 AC: 7 AN: 47292

European-Finnish (FIN) AF: 0.000103 AC: 3 AN: 29056

Middle Eastern (MID) AF: 0.00140 AC: 5 AN: 3568

European-Non Finnish (NFE) AF: 0.00341 AC: 913 AN: 267818

Other (OTH) AF: 0.00287 AC: 75 AN: 26102

GnomAD4 genome AF: 0.00187 AC: 283 AN: 151100 Hom.: 0 Cov.: 32 AF XY: 0.00165 AC XY: 122 AN XY: 73892

African (AFR) AF: 0.000584 AC: 24 AN: 41086

American (AMR) AF: 0.000723 AC: 11 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.00522 AC: 18 AN: 3448

East Asian (EAS) AF: 0.00 AC: 0 AN: 5108

South Asian (SAS) AF: 0.00 AC: 0 AN: 4762

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10576

Middle Eastern (MID) AF: 0.00345 AC: 1 AN: 290

European-Non Finnish (NFE) AF: 0.00333 AC: 225 AN: 67632

Other (OTH) AF: 0.00192 AC: 4 AN: 2082

Alfa AF: 0.00286 Hom.: 0

Bravo AF: 0.00195

ClinVar

ClinVar submissions as Germline

Significance: 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	-0.74
CADD	Benign	8.1
DANN	Benign	0.81
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism

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: rs149138473; hg19: chr16-66471848;