rs4948550

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001080512.3(BICC1):​c.2827T>C​(p.Ser943Pro) variant causes a missense change. The variant allele was found at a frequency of 0.713 in 1,613,224 control chromosomes in the GnomAD database, including 414,483 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S943L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.64 ( 32750 hom., cov: 31)
Exomes 𝑓: 0.72 ( 381733 hom. )

Consequence

BICC1
NM_001080512.3 missense

Scores

18

Clinical Significance

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

Conservation

PhyloP100: 3.61
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]

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=1.4399488E-6).
BP6
Variant 10-58828793-T-C is Benign according to our data. Variant chr10-58828793-T-C is described in ClinVar as [Benign]. Clinvar id is 1297297.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BICC1NM_001080512.3 linkc.2827T>C p.Ser943Pro missense_variant Exon 21 of 21 ENST00000373886.8 NP_001073981.1 Q9H694-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BICC1ENST00000373886.8 linkc.2827T>C p.Ser943Pro missense_variant Exon 21 of 21 1 NM_001080512.3 ENSP00000362993.3 Q9H694-1

Frequencies

GnomAD3 genomes
AF:
0.642
AC:
97494
AN:
151902
Hom.:
32745
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.429
Gnomad AMI
AF:
0.732
Gnomad AMR
AF:
0.717
Gnomad ASJ
AF:
0.605
Gnomad EAS
AF:
0.733
Gnomad SAS
AF:
0.670
Gnomad FIN
AF:
0.721
Gnomad MID
AF:
0.658
Gnomad NFE
AF:
0.734
Gnomad OTH
AF:
0.633
GnomAD2 exomes
AF:
0.707
AC:
176621
AN:
249830
AF XY:
0.708
show subpopulations
Gnomad AFR exome
AF:
0.427
Gnomad AMR exome
AF:
0.788
Gnomad ASJ exome
AF:
0.620
Gnomad EAS exome
AF:
0.743
Gnomad FIN exome
AF:
0.721
Gnomad NFE exome
AF:
0.731
Gnomad OTH exome
AF:
0.709
GnomAD4 exome
AF:
0.720
AC:
1052577
AN:
1461204
Hom.:
381733
Cov.:
46
AF XY:
0.720
AC XY:
523615
AN XY:
726928
show subpopulations
Gnomad4 AFR exome
AF:
0.422
AC:
14105
AN:
33456
Gnomad4 AMR exome
AF:
0.780
AC:
34859
AN:
44698
Gnomad4 ASJ exome
AF:
0.621
AC:
16214
AN:
26122
Gnomad4 EAS exome
AF:
0.733
AC:
29059
AN:
39662
Gnomad4 SAS exome
AF:
0.681
AC:
58704
AN:
86240
Gnomad4 FIN exome
AF:
0.727
AC:
38814
AN:
53372
Gnomad4 NFE exome
AF:
0.733
AC:
814841
AN:
1111528
Gnomad4 Remaining exome
AF:
0.697
AC:
42051
AN:
60368
Heterozygous variant carriers
0
14572
29144
43716
58288
72860
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Exome Hom
Variant carriers
0
19982
39964
59946
79928
99910
<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:
0.642
AC:
97523
AN:
152020
Hom.:
32750
Cov.:
31
AF XY:
0.643
AC XY:
47800
AN XY:
74284
show subpopulations
Gnomad4 AFR
AF:
0.428
AC:
0.428041
AN:
0.428041
Gnomad4 AMR
AF:
0.718
AC:
0.717747
AN:
0.717747
Gnomad4 ASJ
AF:
0.605
AC:
0.605476
AN:
0.605476
Gnomad4 EAS
AF:
0.733
AC:
0.732712
AN:
0.732712
Gnomad4 SAS
AF:
0.669
AC:
0.669432
AN:
0.669432
Gnomad4 FIN
AF:
0.721
AC:
0.721485
AN:
0.721485
Gnomad4 NFE
AF:
0.734
AC:
0.734021
AN:
0.734021
Gnomad4 OTH
AF:
0.634
AC:
0.633869
AN:
0.633869
Heterozygous variant carriers
0
1657
3313
4970
6626
8283
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
0
784
1568
2352
3136
3920
<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:
0.701
Hom.:
184448
Bravo
AF:
0.632
TwinsUK
AF:
0.712
AC:
2640
ALSPAC
AF:
0.724
AC:
2791
ESP6500AA
AF:
0.441
AC:
1943
ESP6500EA
AF:
0.712
AC:
6127
ExAC
AF:
0.700
AC:
84966
Asia WGS
AF:
0.629
AC:
2188
AN:
3478
EpiCase
AF:
0.720
EpiControl
AF:
0.717

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
AlphaMissense
Benign
0.047
BayesDel_addAF
Benign
-0.76
T
BayesDel_noAF
Benign
-0.72
CADD
Benign
15
DANN
Benign
0.36
DEOGEN2
Benign
0.046
T
Eigen
Benign
-0.46
Eigen_PC
Benign
-0.21
FATHMM_MKL
Benign
0.27
N
LIST_S2
Benign
0.65
T
MetaRNN
Benign
0.0000014
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.81
N
PrimateAI
Benign
0.43
T
PROVEAN
Benign
-0.74
N
REVEL
Benign
0.12
Sift
Benign
1.0
T
Sift4G
Benign
0.22
T
Polyphen
0.0
B
Vest4
0.021
MPC
0.27
ClinPred
0.0071
T
GERP RS
3.9
Varity_R
0.13
gMVP
0.46
Mutation Taster
=91/9
polymorphism (auto)

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

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

Other links and lift over

dbSNP: rs4948550; hg19: chr10-60588553; COSMIC: COSV65858952; API