10-58620793-C-T

Position:

• chr10-58620793-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001080512.3(BICC1):​c.191-62C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0409 in 1,525,238 control chromosomes in the GnomAD database, including 1,568 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.031 (125 hom., cov: 32)
  • Exomes 𝑓: 0.042 (1443 hom.)
• Consequence: BICC1 NM_001080512.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.03

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 (BayesDel_noAF=-0.97).
• BP6: Variant 10-58620793-C-T is Benign according to our data. Variant chr10-58620793-C-T is described in ClinVar as [Benign]. Clinvar id is 1247029.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.031 (4717/152112) while in subpopulation NFE AF= 0.0462 (3145/68012). AF 95% confidence interval is 0.0449. There are 125 homozygotes in gnomad4. There are 2290 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 4717 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BICC1	NM_001080512.3	c.191-62C>T		intron_variant		ENST00000373886.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BICC1	ENST00000373886.8	c.191-62C>T		intron_variant		1	NM_001080512.3	P1

Frequencies

GnomAD3 genomes AF: 0.0310 AC: 4716 AN: 151994 Hom.: 125 Cov.: 32

Gnomad AFR AF: 0.00720

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0219

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00520

Gnomad FIN AF: 0.0742

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.0462

Gnomad OTH AF: 0.0273

GnomAD4 exome AF: 0.0420 AC: 57699 AN: 1373126 Hom.: 1443 AF XY: 0.0410 AC XY: 28165 AN XY: 686606

Gnomad4 AFR exome AF: 0.00665

Gnomad4 AMR exome AF: 0.0128

Gnomad4 ASJ exome AF: 0.0169

Gnomad4 EAS exome AF: 0.000129

Gnomad4 SAS exome AF: 0.00704

Gnomad4 FIN exome AF: 0.0775

Gnomad4 NFE exome AF: 0.0480

Gnomad4 OTH exome AF: 0.0346

GnomAD4 genome AF: 0.0310 AC: 4717 AN: 152112 Hom.: 125 Cov.: 32 AF XY: 0.0308 AC XY: 2290 AN XY: 74332

Gnomad4 AFR AF: 0.00718

Gnomad4 AMR AF: 0.0219

Gnomad4 ASJ AF: 0.0150

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00541

Gnomad4 FIN AF: 0.0742

Gnomad4 NFE AF: 0.0462

Gnomad4 OTH AF: 0.0275

Alfa AF: 0.0407 Hom.: 19

Bravo AF: 0.0264

Asia WGS AF: 0.00520 AC: 18 AN: 3478

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	Sep 06, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.0050
DANN	Benign	0.36

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: rs74687990; hg19: chr10-60380553;