chr16-66469802-C-A

Variant names:

• chr16-66469802-C-A
• rs200706119
• NM_001178020.3:c.226C>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.226C>A​(p.Arg76Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0101 in 1,535,802 control chromosomes in the GnomAD database, including 109 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0081 (9 hom., cov: 32)
  • Exomes 𝑓: 0.010 (100 hom.)
• Consequence: BEAN1 NM_001178020.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.76

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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0034638345).
• BP6: Variant 16-66469802-C-A is Benign according to our data. Variant chr16-66469802-C-A is described in ClinVar as [Benign]. Clinvar id is 2646598.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-66469802-C-A is described in Lovd as [Benign].
• BS2: High AC in GnomAd4 at 1231 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BEAN1	NM_001178020.3	c.226C>A	p.Arg76Ser	missense_variant	Exon 3 of 5	ENST00000536005.7	NP_001171491.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BEAN1	ENST00000536005.7	c.226C>A	p.Arg76Ser	missense_variant	Exon 3 of 5	1	NM_001178020.3	ENSP00000442793.2
ENSG00000260851	ENST00000561728.1	n.*523G>T		downstream_gene_variant		2		ENSP00000462196.1

Frequencies

GnomAD3 genomes AF: 0.00809 AC: 1230 AN: 152002 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.00159

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.00301

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00853

Gnomad FIN AF: 0.0261

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0113

Gnomad OTH AF: 0.00576

GnomAD2 exomes AF: 0.00775 AC: 1068 AN: 137830 AF XY: 0.00835

Gnomad AFR exome AF: 0.00170

Gnomad AMR exome AF: 0.00351

Gnomad ASJ exome AF: 0.000963

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0239

Gnomad NFE exome AF: 0.0113

Gnomad OTH exome AF: 0.00740

GnomAD4 exome AF: 0.0103 AC: 14219 AN: 1383682 Hom.: 100 Cov.: 32 AF XY: 0.0102 AC XY: 6956 AN XY: 682786

Gnomad4 AFR exome AF: 0.00123 AC: 39 AN: 31580

Gnomad4 AMR exome AF: 0.00353 AC: 126 AN: 35722

Gnomad4 ASJ exome AF: 0.00119 AC: 30 AN: 25170

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 35730

Gnomad4 SAS exome AF: 0.00785 AC: 622 AN: 79210

Gnomad4 FIN exome AF: 0.0229 AC: 778 AN: 33904

Gnomad4 NFE exome AF: 0.0113 AC: 12147 AN: 1078854

Gnomad4 Remaining exome AF: 0.00760 AC: 440 AN: 57884

GnomAD4 genome AF: 0.00809 AC: 1231 AN: 152120 Hom.: 9 Cov.: 32 AF XY: 0.00910 AC XY: 677 AN XY: 74368

Gnomad4 AFR AF: 0.00159 AC: 0.00159013 AN: 0.00159013

Gnomad4 AMR AF: 0.00301 AC: 0.00301008 AN: 0.00301008

Gnomad4 ASJ AF: 0.000576 AC: 0.000576369 AN: 0.000576369

Gnomad4 EAS AF: 0.000194 AC: 0.000193648 AN: 0.000193648

Gnomad4 SAS AF: 0.00874 AC: 0.00874271 AN: 0.00874271

Gnomad4 FIN AF: 0.0261 AC: 0.0261025 AN: 0.0261025

Gnomad4 NFE AF: 0.0113 AC: 0.0113138 AN: 0.0113138

Gnomad4 OTH AF: 0.00570 AC: 0.00569801 AN: 0.00569801

Alfa AF: 0.00398 Hom.: 0

Bravo AF: 0.00603

TwinsUK AF: 0.00593 AC: 22

ALSPAC AF: 0.0106 AC: 41

ExAC AF: 0.00444 AC: 259

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jan 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

BEAN1: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.50	T
MetaRNN	Benign	0.0035	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.063
Sift	Benign	0.11	T
Sift4G	Benign	0.31	T
Vest4		0.38
MVP		0.099
ClinPred		0.016	T
GERP RS		4.1
Varity_R		0.17
gMVP		0.23
Mutation Taster		=98/2	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

Publications

LitVar

Other links and lift over

dbSNP: rs200706119; hg19: chr16-66503705; COSMIC: COSV104607009; COSMIC: COSV104607009;