chr16-66437945-G-A

Position:

• chr16-66437945-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 2646594.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 283 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BEAN1	NM_001178020.3	c.25+244G>A		intron_variant		ENST00000536005.7	NP_001171491.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BEAN1	ENST00000536005.7	c.25+244G>A		intron_variant		1	NM_001178020.3	ENSP00000442793.2

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

Gnomad4 AFR exome AF: 0.000685

Gnomad4 AMR exome AF: 0.000807

Gnomad4 ASJ exome AF: 0.00657

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000148

Gnomad4 FIN exome AF: 0.000103

Gnomad4 NFE exome AF: 0.00341

Gnomad4 OTH exome AF: 0.00287

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

Gnomad4 AFR AF: 0.000584

Gnomad4 AMR AF: 0.000723

Gnomad4 ASJ AF: 0.00522

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00333

Gnomad4 OTH AF: 0.00192

Alfa AF: 0.00286 Hom.: 0

Bravo AF: 0.00195

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2022

BEAN1: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	8.1
DANN	Benign	0.81

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: rs149138473; hg19: chr16-66471848;