10-58776160-T-C

Variant names:

• chr10-58776160-T-C
• rs999845
• NM_001080512.3:c.308-8841T>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.308-8841T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.782 in 152,140 control chromosomes in the GnomAD database, including 46,974 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 0.78 (46974 hom., cov: 32)
• Consequence: BICC1 NM_001080512.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.107
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 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.308-8841T>C		intron	N/A	NP_001073981.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BICC1	ENST00000373886.8	TSL:1 MANE Select	c.308-8841T>C		intron	N/A	ENSP00000362993.3

Frequencies

GnomAD3 genomes AF: 0.782 AC: 118863 AN: 152022 Hom.: 46945 Cov.: 32

Gnomad AFR AF: 0.675

Gnomad AMI AF: 0.900

Gnomad AMR AF: 0.866

Gnomad ASJ AF: 0.878

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.847

Gnomad FIN AF: 0.841

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.790

Gnomad OTH AF: 0.809

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

GnomAD4 genome AF: 0.782 AC: 118935 AN: 152140 Hom.: 46974 Cov.: 32 AF XY: 0.786 AC XY: 58453 AN XY: 74380

African (AFR) AF: 0.675 AC: 27996 AN: 41468

American (AMR) AF: 0.866 AC: 13248 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.878 AC: 3047 AN: 3472

East Asian (EAS) AF: 0.996 AC: 5150 AN: 5172

South Asian (SAS) AF: 0.846 AC: 4082 AN: 4824

European-Finnish (FIN) AF: 0.841 AC: 8916 AN: 10602

Middle Eastern (MID) AF: 0.867 AC: 255 AN: 294

European-Non Finnish (NFE) AF: 0.790 AC: 53708 AN: 67986

Other (OTH) AF: 0.811 AC: 1712 AN: 2110

Alfa AF: 0.797 Hom.: 82608

Bravo AF: 0.782

Asia WGS AF: 0.924 AC: 3209 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.2
DANN	Benign	0.62
PhyloP100		-0.11
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: rs999845; hg19: chr10-60535920;