NM_001080512.3:c.2181+632A>T

Variant names:

• chr10-58803874-A-T
• rs11006267
• NM_001080512.3:c.2181+632A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001080512.3(BICC1):​c.2181+632A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00375 in 152,338 control chromosomes in the GnomAD database, including 3 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 0.0037 (3 hom., cov: 33)
• Consequence: BICC1 NM_001080512.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.127
• Publications: 6 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=-0.85).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00375 (571/152338) while in subpopulation NFE AF = 0.00651 (443/68028). AF 95% confidence interval is 0.00601. There are 3 homozygotes in GnomAd4. There are 263 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 571 AD,Unknown gene.

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.2181+632A>T		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.2181+632A>T		intron	N/A	ENSP00000362993.3
	BICC1	ENST00000263103.1	TSL:1	c.1059+632A>T		intron	N/A	ENSP00000263103.1

Frequencies

GnomAD3 genomes AF: 0.00375 AC: 571 AN: 152220 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00169

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.000785

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00198

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00651

Gnomad OTH AF: 0.00143

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

GnomAD4 genome AF: 0.00375 AC: 571 AN: 152338 Hom.: 3 Cov.: 33 AF XY: 0.00353 AC XY: 263 AN XY: 74492

African (AFR) AF: 0.00168 AC: 70 AN: 41588

American (AMR) AF: 0.000784 AC: 12 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000828 AC: 4 AN: 4832

European-Finnish (FIN) AF: 0.00198 AC: 21 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00651 AC: 443 AN: 68028

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.000139 Hom.: 159

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.56
DANN	Benign	0.42
PhyloP100		-0.13

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: rs11006267; hg19: chr10-60563634;