10-58527875-G-C

Variant names:

• chr10-58527875-G-C
• rs1346300
• NM_001080512.3:c.190+14542G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080512.3(BICC1):​c.190+14542G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 151,716 control chromosomes in the GnomAD database, including 17,110 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.46 (17110 hom., cov: 31)
• Consequence: BICC1 NM_001080512.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.794
• Publications: 9 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BICC1	NM_001080512.3	c.190+14542G>C		intron_variant	Intron 1 of 20	ENST00000373886.8	NP_001073981.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BICC1	ENST00000373886.8	c.190+14542G>C		intron_variant	Intron 1 of 20	1	NM_001080512.3	ENSP00000362993.3

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69760 AN: 151598 Hom.: 17094 Cov.: 31

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.667

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.520

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.519

Gnomad OTH AF: 0.463

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.460 AC: 69784 AN: 151716 Hom.: 17110 Cov.: 31 AF XY: 0.459 AC XY: 34051 AN XY: 74136

African (AFR) AF: 0.290 AC: 12009 AN: 41430

American (AMR) AF: 0.624 AC: 9510 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.496 AC: 1717 AN: 3462

East Asian (EAS) AF: 0.521 AC: 2662 AN: 5110

South Asian (SAS) AF: 0.454 AC: 2178 AN: 4800

European-Finnish (FIN) AF: 0.453 AC: 4781 AN: 10548

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.519 AC: 35221 AN: 67824

Other (OTH) AF: 0.459 AC: 965 AN: 2104

Alfa AF: 0.336 Hom.: 886

Bravo AF: 0.471

Asia WGS AF: 0.436 AC: 1519 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.4
DANN	Benign	0.65
PhyloP100		-0.79
Mutation Taster		=100/0	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: rs1346300; hg19: chr10-60287635;