rs4948550

Variant names:

• chr10-58828793-T-C
• rs4948550
• NM_001080512.3:c.2827T>C

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 3.61
• Publications: 39 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

ENSG00000301981 (HGNC:):

ACMG classification

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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080512.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BICC1	NM_001080512.3	MANE Select	c.2827T>C	p.Ser943Pro	missense	Exon 21 of 21	NP_001073981.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BICC1	ENST00000373886.8	TSL:1 MANE Select	c.2827T>C	p.Ser943Pro	missense	Exon 21 of 21	ENSP00000362993.3
	ENSG00000301981	ENST00000783190.1		n.210-8831A>G		intron	N/A

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

GnomAD2 exomes AF: 0.707 AC: 176621 AN: 249830 AF XY: 0.708

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

African (AFR) AF: 0.422 AC: 14105 AN: 33456

American (AMR) AF: 0.780 AC: 34859 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.621 AC: 16214 AN: 26122

East Asian (EAS) AF: 0.733 AC: 29059 AN: 39662

South Asian (SAS) AF: 0.681 AC: 58704 AN: 86240

European-Finnish (FIN) AF: 0.727 AC: 38814 AN: 53372

Middle Eastern (MID) AF: 0.683 AC: 3930 AN: 5758

European-Non Finnish (NFE) AF: 0.733 AC: 814841 AN: 1111528

Other (OTH) AF: 0.697 AC: 42051 AN: 60368

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

African (AFR) AF: 0.428 AC: 17738 AN: 41440

American (AMR) AF: 0.718 AC: 10960 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.605 AC: 2101 AN: 3470

East Asian (EAS) AF: 0.733 AC: 3772 AN: 5148

South Asian (SAS) AF: 0.669 AC: 3228 AN: 4822

European-Finnish (FIN) AF: 0.721 AC: 7616 AN: 10556

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.734 AC: 49909 AN: 67994

Other (OTH) AF: 0.634 AC: 1340 AN: 2114

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		3.6
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

Other links and lift over

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