rs4783595

Positions:

• chr16-66456691-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001178020.3(BEAN1):​c.26-12911T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 152,202 control chromosomes in the GnomAD database, including 1,528 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (1528 hom., cov: 32)
• Consequence: BEAN1 NM_001178020.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BEAN1	NM_001178020.3	c.26-12911T>C		intron_variant		ENST00000536005.7	NP_001171491.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BEAN1	ENST00000536005.7	c.26-12911T>C		intron_variant		1	NM_001178020.3	ENSP00000442793	P1
BEAN1	ENST00000299694.12	c.-302-12911T>C		intron_variant		1		ENSP00000299694
BEAN1	ENST00000561796.5	n.62-12911T>C		intron_variant, non_coding_transcript_variant		1
BEAN1	ENST00000562849.6	c.-302-12911T>C		intron_variant, NMD_transcript_variant		2		ENSP00000456822

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20160 AN: 152080 Hom.: 1528 Cov.: 32

Gnomad AFR AF: 0.0963

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.129

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.133 AC: 20173 AN: 152202 Hom.: 1528 Cov.: 32 AF XY: 0.137 AC XY: 10216 AN XY: 74418

Gnomad4 AFR AF: 0.0964

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.223

Gnomad4 SAS AF: 0.257

Gnomad4 FIN AF: 0.172

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.130

Alfa AF: 0.141 Hom.: 853

Bravo AF: 0.128

Asia WGS AF: 0.197 AC: 686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.042
DANN	Benign	0.34

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: rs4783595; hg19: chr16-66490594;