rs4948550

chr10-58828793-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S943L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.64 (32750 hom., cov: 31)
  • Exomes 𝑓: 0.72 (381733 hom.)
• Consequence: BICC1 NM_001080512.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.61

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
BICC1	NM_001080512.3	c.2827T>C	p.Ser943Pro	missense_variant	21/21	ENST00000373886.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BICC1	ENST00000373886.8	c.2827T>C	p.Ser943Pro	missense_variant	21/21	1	NM_001080512.3	P1

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97494 AN: 151902 Hom.: 32745 Cov.: 31

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

GnomAD3 exomes AF: 0.707 AC: 176621 AN: 249830 Hom.: 63471 AF XY: 0.708 AC XY: 95708 AN XY: 135120

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 SAS exome AF: 0.672

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

Gnomad4 AFR exome AF: 0.422

Gnomad4 AMR exome AF: 0.780

Gnomad4 ASJ exome AF: 0.621

Gnomad4 EAS exome AF: 0.733

Gnomad4 SAS exome AF: 0.681

Gnomad4 FIN exome AF: 0.727

Gnomad4 NFE exome AF: 0.733

Gnomad4 OTH exome AF: 0.697

GnomAD4 genome AF: 0.642 AC: 97523 AN: 152020 Hom.: 32750 Cov.: 31 AF XY: 0.643 AC XY: 47800 AN XY: 74284

Gnomad4 AFR AF: 0.428

Gnomad4 AMR AF: 0.718

Gnomad4 ASJ AF: 0.605

Gnomad4 EAS AF: 0.733

Gnomad4 SAS AF: 0.669

Gnomad4 FIN AF: 0.721

Gnomad4 NFE AF: 0.734

Gnomad4 OTH AF: 0.634

Alfa AF: 0.709 Hom.: 97060

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

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
MutationTaster	Benign	0.86	P
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

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

Other links and lift over

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