ENST00000263103.1:c.1418G>C

Variant names:

• chr10-58813993-G-C
• rs9416746
• ENST00000263103.1:c.1418G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000263103.1(BICC1):​c.1418G>C​(p.Arg473Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R473L) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: BICC1 ENST00000263103.1 missense
• Scores: Splicing: ADA: 0.00001886
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.226
• Publications: 16 publications found

Genes affected

BICC1 (HGNC:19351): (BicC family RNA binding protein 1) This gene encodes an RNA-binding protein that is active in regulating gene expression by modulating protein translation during embryonic development. Mouse studies identified the corresponding protein to be under strict control during cell differentiation and to be a maternally provided gene product. [provided by RefSeq, Apr 2009]

BICC1 Gene-Disease associations (from GenCC):

• renal dysplasia, cystic, susceptibility to

  Inheritance: AD, Unknown Classification: MODERATE, LIMITED Submitted by: Broad Center for Mendelian Genomics, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.084307164).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000263103.1. 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
	BICC1	NM_001080512.3	MANE Select	c.2533+7G>C		splice_region intron	N/A	NP_001073981.1	Q9H694-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BICC1	ENST00000263103.1	TSL:1	c.1418G>C	p.Arg473Pro	missense	Exon 10 of 10	ENSP00000263103.1	A6NGY7
	BICC1	ENST00000373886.8	TSL:1 MANE Select	c.2533+7G>C		splice_region intron	N/A	ENSP00000362993.3	Q9H694-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 52

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	8.4
DANN	Uncertain	0.98
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.23
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.065
Sift	Uncertain	0.012	D
Sift4G	Benign	0.089	T
Vest4		0.075
MutPred		0.41		Loss of sheet (P = 0.0228)
MVP		0.13
ClinPred		0.086	T
GERP RS		4.4
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000019
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.010		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: rs9416746; hg19: chr10-60573753; COSMIC: COSV54066870;