Genetic Variant BICC1:p.Arg473Leu (chr10-58813993-G-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000263103.1(BICC1):c.1418G>T(p.Arg473Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.742 in 1,613,242 control chromosomes in the GnomAD database, including 445,413 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.76 ( 43903 hom., cov: 33)

Exomes 𝑓: 0.74 ( 401510 hom. )

Consequence

BICC1
ENST00000263103.1 missense

Scores

Splicing: ADA: 0.0004741

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.226

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.4960933E-7).

BP6

Variant 10-58813993-G-T is Benign according to our data. Variant chr10-58813993-G-T is described in ClinVar as [Benign]. Clinvar id is 1231983.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.802 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BICC1	NM_001080512.3 link	c.2533+7G>T		splice_region_variant, intron_variant	Intron 18 of 20	ENST00000373886.8	NP_001073981.1	Q9H694-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BICC1	ENST00000263103.1 link	c.1418G>T	p.Arg473Leu	missense_variant	Exon 10 of 10	1		ENSP00000263103.1		A6NGY7
BICC1	ENST00000373886.8 link	c.2533+7G>T		splice_region_variant, intron_variant	Intron 18 of 20	1	NM_001080512.3	ENSP00000362993.3		Q9H694-1

Frequencies

GnomAD3 genomes

AF:

0.758

AC:

115231

AN:

151994

Hom.:

43857

Cov.:

show subpopulations

Gnomad AFR

AF:

0.809

Gnomad AMI

AF:

0.732

Gnomad AMR

AF:

0.764

Gnomad ASJ

AF:

0.608

Gnomad EAS

AF:

0.753

Gnomad SAS

AF:

0.713

Gnomad FIN

AF:

0.732

Gnomad MID

AF:

0.703

Gnomad NFE

AF:

0.743

Gnomad OTH

AF:

0.728

GnomAD3 exomes

AF:

0.746

AC:

187482

AN:

251222

Hom.:

70260

AF XY:

0.741

AC XY:

100591

AN XY:

135768

show subpopulations

Gnomad AFR exome

AF:

0.810

Gnomad AMR exome

AF:

0.812

Gnomad ASJ exome

AF:

0.624

Gnomad EAS exome

AF:

0.754

Gnomad SAS exome

AF:

0.714

Gnomad FIN exome

AF:

0.731

Gnomad NFE exome

AF:

0.739

Gnomad OTH exome

AF:

0.731

GnomAD4 exome

AF:

0.741

AC:

1082058

AN:

1461130

Hom.:

401510

Cov.:

AF XY:

0.740

AC XY:

537877

AN XY:

726904

show subpopulations

Gnomad4 AFR exome

AF:

0.813

Gnomad4 AMR exome

AF:

0.805

Gnomad4 ASJ exome

AF:

0.626

Gnomad4 EAS exome

AF:

0.746

Gnomad4 SAS exome

AF:

0.720

Gnomad4 FIN exome

AF:

0.739

Gnomad4 NFE exome

AF:

0.740

Gnomad4 OTH exome

AF:

0.733

GnomAD4 genome

AF:

0.758

AC:

115334

AN:

152112

Hom.:

43903

Cov.:

AF XY:

0.757

AC XY:

56280

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.809

Gnomad4 AMR

AF:

0.765

Gnomad4 ASJ

AF:

0.608

Gnomad4 EAS

AF:

0.753

Gnomad4 SAS

AF:

0.712

Gnomad4 FIN

AF:

0.732

Gnomad4 NFE

AF:

0.743

Gnomad4 OTH

AF:

0.730

Alfa

AF:

0.737

Hom.:

32927

Bravo

AF:

0.763

TwinsUK

AF:

0.722

AC:

2678

ALSPAC

AF:

0.731

AC:

2818

ESP6500AA

AF:

0.808

AC:

3561

ESP6500EA

AF:

0.722

AC:

6209

ExAC

AF:

0.747

AC:

90641

Asia WGS

AF:

0.707

AC:

2459

AN:

3478

EpiCase

AF:

0.728

EpiControl

AF:

0.723

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.73

CADD

Benign

8.7

DANN

Uncertain

0.99

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.26

MetaRNN

Benign

9.5e-7

MetaSVM

Benign

-1.0

PROVEAN

Benign

0.66

REVEL

Benign

0.043

Sift

Uncertain

0.014

Sift4G

Benign

0.13

Vest4

0.022

ClinPred

0.010

GERP RS

4.4

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00047

dbscSNV1_RF

Benign

0.022

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over