16-66469788-GCCACCGCCA-G

Position:

• chr16-66469788-GCCACCGCCA-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The ENST00000536005.7(BEAN1):​c.227_235del​(p.Arg76_His78del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000371 in 1,535,636 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00024 (0 hom.)
• Consequence: BEAN1 ENST00000536005.7 inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 1.35

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

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 16-66469788-GCCACCGCCA-G is Benign according to our data. Variant chr16-66469788-GCCACCGCCA-G is described in ClinVar as [Benign]. Clinvar id is 3053333.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 234 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BEAN1	NM_001178020.3	c.227_235del	p.Arg76_His78del	inframe_deletion	3/5	ENST00000536005.7	NP_001171491.1
LOC124903698	XM_047435016.1	c.*5309_*5317del		3_prime_UTR_variant	5/5		XP_047290972.1
BEAN1-AS1	NR_109960.1			non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BEAN1	ENST00000536005.7	c.227_235del	p.Arg76_His78del	inframe_deletion	3/5	1	NM_001178020.3	ENSP00000442793	P1

Frequencies

GnomAD3 genomes AF: 0.00153 AC: 232 AN: 151884 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00496

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000590

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.000624 AC: 86 AN: 137870 Hom.: 0 AF XY: 0.000655 AC XY: 49 AN XY: 74788

Gnomad AFR exome AF: 0.00636

Gnomad AMR exome AF: 0.000776

Gnomad ASJ exome AF: 0.000843

Gnomad EAS exome AF: 0.000285

Gnomad SAS exome AF: 0.0000890

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000215

Gnomad OTH exome AF: 0.000478

GnomAD4 exome AF: 0.000242 AC: 335 AN: 1383634 Hom.: 0 AF XY: 0.000243 AC XY: 166 AN XY: 682734

Gnomad4 AFR exome AF: 0.00525

Gnomad4 AMR exome AF: 0.000728

Gnomad4 ASJ exome AF: 0.000715

Gnomad4 EAS exome AF: 0.000168

Gnomad4 SAS exome AF: 0.000114

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000751

Gnomad4 OTH exome AF: 0.000449

GnomAD4 genome AF: 0.00154 AC: 234 AN: 152002 Hom.: 0 Cov.: 32 AF XY: 0.00144 AC XY: 107 AN XY: 74306

Gnomad4 AFR AF: 0.00497

Gnomad4 AMR AF: 0.000589

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00143

Alfa AF: 0.000336 Hom.: 0

Bravo AF: 0.00192

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

BEAN1-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 22, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2024

BEAN1: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs564817056; hg19: chr16-66503691;