NM_001178020.3:c.90T>C

Variant names:

• chr16-66469666-T-C
• rs529552966
• NM_001178020.3:c.90T>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001178020.3(BEAN1):​c.90T>C​(p.His30His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,383,542 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: BEAN1 NM_001178020.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.870
• Publications: 0 publications found

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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP7: Synonymous conserved (PhyloP=-0.87 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001178020.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BEAN1	NM_001178020.3	MANE Select	c.90T>C	p.His30His	synonymous	Exon 3 of 5	NP_001171491.1	Q3B7T3-1
	BEAN1	NM_001136106.5		c.-238T>C		5_prime_UTR	Exon 2 of 4	NP_001129578.1	Q3B7T3-2
	BEAN1	NM_001197224.4		c.-238T>C		5_prime_UTR	Exon 2 of 5	NP_001184153.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BEAN1	ENST00000536005.7	TSL:1 MANE Select	c.90T>C	p.His30His	synonymous	Exon 3 of 5	ENSP00000442793.2	Q3B7T3-1
	BEAN1	ENST00000299694.12	TSL:1	c.-238T>C		5_prime_UTR	Exon 2 of 4	ENSP00000299694.8	Q3B7T3-2
	BEAN1	ENST00000561796.5	TSL:1	n.126T>C		non_coding_transcript_exon	Exon 2 of 5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000145 AC: 2 AN: 1383542 Hom.: 0 Cov.: 31 AF XY: 0.00000146 AC XY: 1 AN XY: 682738

African (AFR) AF: 0.00 AC: 0 AN: 31588

American (AMR) AF: 0.00 AC: 0 AN: 35698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35734

South Asian (SAS) AF: 0.00 AC: 0 AN: 79234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33902

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 0.00000185 AC: 2 AN: 1078618

Other (OTH) AF: 0.00 AC: 0 AN: 57892

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.3
DANN	Benign	0.57
PhyloP100		-0.87
PromoterAI		-0.055	Neutral

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

Other links and lift over

dbSNP: rs529552966; hg19: chr16-66503569;