dbSNP rs9416746: BICC1:p.Arg473Leu (chr10-58813993-G-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -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. 14/18 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

Publications

16 publications found

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 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

BICC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

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>T		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>T	p.Arg473Leu	missense	Exon 10 of 10	ENSP00000263103.1	A6NGY7
	BICC1	ENST00000373886.8	TSL:1 MANE Select	c.2533+7G>T		splice_region intron	N/A	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

GnomAD2 exomes

AF:

0.746

AC:

187482

AN:

251222

AF XY:

0.741

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 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

African (AFR)

AF:

0.813

AC:

27199

AN:

33458

American (AMR)

AF:

0.805

AC:

35999

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.626

AC:

16359

AN:

26120

East Asian (EAS)

AF:

0.746

AC:

29583

AN:

39656

South Asian (SAS)

AF:

0.720

AC:

62092

AN:

86242

European-Finnish (FIN)

AF:

0.739

AC:

39452

AN:

53418

Middle Eastern (MID)

AF:

0.724

AC:

4177

AN:

5766

European-Non Finnish (NFE)

AF:

0.740

AC:

822918

AN:

1111394

Other (OTH)

AF:

0.733

AC:

44279

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

15678

31356

47035

62713

78391

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20160

40320

60480

80640

100800

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.758

AC:

115334

AN:

152112

Hom.:

43903

Cov.:

AF XY:

0.757

AC XY:

56280

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.809

AC:

33604

AN:

41526

American (AMR)

AF:

0.765

AC:

11692

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.608

AC:

2110

AN:

3470

East Asian (EAS)

AF:

0.753

AC:

3870

AN:

5142

South Asian (SAS)

AF:

0.712

AC:

3434

AN:

4824

European-Finnish (FIN)

AF:

0.732

AC:

7741

AN:

10578

Middle Eastern (MID)

AF:

0.697

AC:

205

AN:

294

European-Non Finnish (NFE)

AF:

0.743

AC:

50470

AN:

67966

Other (OTH)

AF:

0.730

AC:

1540

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1474

2947

4421

5894

7368

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

860

1720

2580

3440

4300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.743

Hom.:

99377

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.73

CADD

Benign

8.7

(source)

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

PhyloP100

0.23

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

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over