chr10-58513048-C-T

Position:

• chr10-58513048-C-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

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
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.629

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 -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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2046 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BICC1	NM_001080512.3	c.-96C>T		5_prime_UTR_variant	1/21	ENST00000373886.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BICC1	ENST00000373886.8	c.-96C>T		5_prime_UTR_variant	1/21	1	NM_001080512.3	P1

Frequencies

GnomAD3 genomes AF: 0.0136 AC: 2047 AN: 150362 Hom.: 27 Cov.: 33

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

Gnomad4 AFR exome AF: 0.00226

Gnomad4 AMR exome AF: 0.0110

Gnomad4 ASJ exome AF: 0.0162

Gnomad4 EAS exome AF: 0.000140

Gnomad4 SAS exome AF: 0.0417

Gnomad4 FIN exome AF: 0.0459

Gnomad4 NFE exome AF: 0.0147

Gnomad4 OTH exome AF: 0.0152

GnomAD4 genome AF: 0.0136 AC: 2046 AN: 150468 Hom.: 27 Cov.: 33 AF XY: 0.0151 AC XY: 1107 AN XY: 73496

Gnomad4 AFR AF: 0.00227

Gnomad4 AMR AF: 0.00754

Gnomad4 ASJ AF: 0.0220

Gnomad4 EAS AF: 0.000195

Gnomad4 SAS AF: 0.0355

Gnomad4 FIN AF: 0.0427

Gnomad4 NFE AF: 0.0166

Gnomad4 OTH AF: 0.0144

Alfa AF: 0.00850 Hom.: 3

Bravo AF: 0.0100

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 13, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	17
DANN	Uncertain	0.97

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs572664020; hg19: chr10-60272808;