16-66447543-C-T

Position:

• chr16-66447543-C-T

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+9842C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0057 in 152,176 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.0057 (4 hom., cov: 32)
• Consequence: BEAN1 NM_001178020.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.290

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=-0.93).
• BP6: Variant 16-66447543-C-T is Benign according to our data. Variant chr16-66447543-C-T is described in ClinVar as [Benign]. Clinvar id is 2646595.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 868 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BEAN1	NM_001178020.3	c.25+9842C>T		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+9842C>T		intron_variant		1	NM_001178020.3	ENSP00000442793	P1
BEAN1	ENST00000299694.12	c.-303+20112C>T		intron_variant		1		ENSP00000299694
BEAN1	ENST00000561796.5	n.61+20112C>T		intron_variant, non_coding_transcript_variant		1
BEAN1	ENST00000562849.6	c.-303+20112C>T		intron_variant, NMD_transcript_variant		2		ENSP00000456822

Frequencies

GnomAD3 genomes AF: 0.00571 AC: 868 AN: 152058 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00104

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00550

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.0236

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.00671

Gnomad OTH AF: 0.00287

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

GnomAD4 genome AF: 0.00570 AC: 868 AN: 152176 Hom.: 4 Cov.: 32 AF XY: 0.00636 AC XY: 473 AN XY: 74400

Gnomad4 AFR AF: 0.00104

Gnomad4 AMR AF: 0.00549

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00332

Gnomad4 FIN AF: 0.0236

Gnomad4 NFE AF: 0.00669

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00554 Hom.: 2

Bravo AF: 0.00396

Asia WGS AF: 0.00202 AC: 7 AN: 3478

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

Dec 01, 2022

BEAN1: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.37
DANN	Benign	0.38

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: rs188932587; hg19: chr16-66481446;