Genetic Variant BICC1:c.-96C>T (chr10-58513048-C-T) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_001080512.3(BICC1):c.-96C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0152 in 980,452 control chromosomes in the GnomAD database, including 167 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 27 hom., cov: 33)

Exomes 𝑓: 0.016 ( 140 hom. )

Consequence

BICC1
NM_001080512.3 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.629

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 was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 10-58513048-C-T is Benign according to our data. Variant chr10-58513048-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1219757.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0136 (2046/150468) while in subpopulation SAS AF = 0.0355 (171/4816). AF 95% confidence interval is 0.0312. There are 27 homozygotes in GnomAd4. There are 1107 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position FAILED quality control check.

BS2

High AC in GnomAd4 at 2046 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BICC1	NM_001080512.3 link	c.-96C>T		5_prime_UTR_variant	Exon 1 of 21	ENST00000373886.8	NP_001073981.1	Q9H694-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BICC1	ENST00000373886 link	c.-96C>T		5_prime_UTR_variant	Exon 1 of 21	1	NM_001080512.3	ENSP00000362993.3		Q9H694-1

Frequencies

GnomAD3 genomes

AF:

0.0136

AC:

2047

AN:

150362

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00228

Gnomad AMI

AF:

0.00440

Gnomad AMR

AF:

0.00755

Gnomad ASJ

AF:

0.0220

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.0357

Gnomad FIN

AF:

0.0427

Gnomad MID

AF:

0.0414

Gnomad NFE

AF:

0.0166

Gnomad OTH

AF:

0.0145

GnomAD4 exome

AF:

0.0155

AC:

12868

AN:

829984

Hom.:

140

AF XY:

0.0159

AC XY:

6365

AN XY:

400118

show subpopulations

Gnomad4 AFR exome

AF:

0.00226

AC:

AN:

16788

Gnomad4 AMR exome

AF:

0.0110

AC:

AN:

6712

Gnomad4 ASJ exome

AF:

0.0162

AC:

179

AN:

11038

Gnomad4 EAS exome

AF:

0.000140

AC:

AN:

21474

Gnomad4 SAS exome

AF:

0.0417

AC:

727

AN:

17444

Gnomad4 FIN exome

AF:

0.0459

AC:

1020

AN:

22204

Gnomad4 NFE exome

AF:

0.0147

AC:

10269

AN:

698234

Gnomad4 Remaining exome

AF:

0.0152

AC:

514

AN:

33772

Heterozygous variant carriers

582

1164

1746

2328

2910

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

428

856

1284

1712

2140

<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:

0.0136

AC:

2046

AN:

150468

Hom.:

Cov.:

AF XY:

0.0151

AC XY:

1107

AN XY:

73496

show subpopulations

Gnomad4 AFR

AF:

0.00227

AC:

0.00227394

AN:

0.00227394

Gnomad4 AMR

AF:

0.00754

AC:

0.00754367

AN:

0.00754367

Gnomad4 ASJ

AF:

0.0220

AC:

0.022029

AN:

0.022029

Gnomad4 EAS

AF:

0.000195

AC:

0.000195389

AN:

0.000195389

Gnomad4 SAS

AF:

0.0355

AC:

0.0355066

AN:

0.0355066

Gnomad4 FIN

AF:

0.0427

AC:

0.0427039

AN:

0.0427039

Gnomad4 NFE

AF:

0.0166

AC:

0.0166173

AN:

0.0166173

Gnomad4 OTH

AF:

0.0144

AC:

0.0143541

AN:

0.0143541

Heterozygous variant carriers

111

222

334

445

556

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.00850

Hom.:

Bravo

AF:

0.0100

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 13, 2020

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

0.97

Splicing

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