NM_001178020.3:c.501A>G

Variant names:

• chr16-66480646-A-G
• rs141546513
• NM_001178020.3:c.501A>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001178020.3(BEAN1):​c.501A>G​(p.Pro167Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0014 in 1,551,428 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00086 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0015 (3 hom.)
• Consequence: BEAN1 NM_001178020.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -3.12
• Publications: 1 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]

ENSG00000260851 (HGNC:):

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

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 16-66480646-A-G is Benign according to our data. Variant chr16-66480646-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2672642.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.12 with no splicing effect.
• BS2: High AC in GnomAd4 at 131 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.501A>G	p.Pro167Pro	synonymous	Exon 5 of 5	NP_001171491.1	Q3B7T3-1
	BEAN1	NM_001136106.5		c.174A>G	p.Pro58Pro	synonymous	Exon 4 of 4	NP_001129578.1	Q3B7T3-2
	BEAN1	NM_001197224.4		c.114-2232A>G		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.501A>G	p.Pro167Pro	synonymous	Exon 5 of 5	ENSP00000442793.2	Q3B7T3-1
	BEAN1	ENST00000299694.12	TSL:1	c.174A>G	p.Pro58Pro	synonymous	Exon 4 of 4	ENSP00000299694.8	Q3B7T3-2
	ENSG00000260851	ENST00000561728.1	TSL:2	n.*11+518T>C		intron	N/A	ENSP00000462196.1	J3KRW8

Frequencies

GnomAD3 genomes AF: 0.000861 AC: 131 AN: 152100 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00134

Gnomad OTH AF: 0.000958

GnomAD2 exomes AF: 0.000868 AC: 135 AN: 155520 AF XY: 0.000994

Gnomad AFR exome AF: 0.000126

Gnomad AMR exome AF: 0.000568

Gnomad ASJ exome AF: 0.000591

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000425

Gnomad NFE exome AF: 0.00162

Gnomad OTH exome AF: 0.00160

GnomAD4 exome AF: 0.00146 AC: 2037 AN: 1399210 Hom.: 3 Cov.: 31 AF XY: 0.00143 AC XY: 989 AN XY: 690126

African (AFR) AF: 0.000190 AC: 6 AN: 31598

American (AMR) AF: 0.000560 AC: 20 AN: 35684

Ashkenazi Jewish (ASJ) AF: 0.000358 AC: 9 AN: 25160

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

South Asian (SAS) AF: 0.0000884 AC: 7 AN: 79216

European-Finnish (FIN) AF: 0.000264 AC: 13 AN: 49278

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5692

European-Non Finnish (NFE) AF: 0.00178 AC: 1925 AN: 1078844

Other (OTH) AF: 0.000965 AC: 56 AN: 58004

GnomAD4 genome AF: 0.000861 AC: 131 AN: 152218 Hom.: 0 Cov.: 33 AF XY: 0.000833 AC XY: 62 AN XY: 74428

African (AFR) AF: 0.000385 AC: 16 AN: 41532

American (AMR) AF: 0.00118 AC: 18 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

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

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10612

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

European-Non Finnish (NFE) AF: 0.00134 AC: 91 AN: 67992

Other (OTH) AF: 0.000948 AC: 2 AN: 2110

Alfa AF: 0.000960 Hom.: 0

Bravo AF: 0.000937

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	BEAN1-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.27
DANN	Benign	0.69
PhyloP100		-3.1
Mutation Taster		=97/3	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: rs141546513; hg19: chr16-66514549;