rs745483989

chr19-47695362-CAGG-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PVS1_Moderate PP3_Moderate BP6_Moderate

The NM_001394372.1(BICRA):c.3077-2_3077del variant causes a splice acceptor, coding sequence change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.028 (0 hom., cov: 0)
  • Exomes 𝑓: 0.013 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BICRA NM_001394372.1 splice_acceptor, coding_sequence
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.23

Genes affected

BICRA (HGNC:4332): (BRD4 interacting chromatin remodeling complex associated protein) Enables transcription regulator activator activity. Involved in positive regulation of transcription, DNA-templated. Located in nucleus. Part of SWI/SNF complex. Implicated in Coffin-Siris syndrome. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PVS1: Splicing variant, NOT destroyed by nmd, known LOF gene, truncates exone, which is 0.023275677 fraction of the gene. Cryptic splice site detected, with MaxEntScore 9.9, offset of 18, new splice context is: cctccctcctctgcttccAGccg. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.
• PP3: Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• BP6: Variant 19-47695362-CAGG-C is Benign according to our data. Variant chr19-47695362-CAGG-C is described in ClinVar as [Benign]. Clinvar id is 402903.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BICRA	NM_001394372.1	c.3077-2_3077del		splice_acceptor_variant, coding_sequence_variant	10/15	ENST00000594866.3
BICRA	NM_015711.3	c.3077-2_3077del		splice_acceptor_variant, coding_sequence_variant	10/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BICRA	ENST00000594866.3	c.3077-2_3077del		splice_acceptor_variant, coding_sequence_variant	10/15	2	NM_001394372.1	P2
	ENST00000599924.1	n.87-36702_87-36700del		intron_variant, non_coding_transcript_variant		5
BICRA	ENST00000396720.7	c.3077-2_3077del		splice_acceptor_variant, coding_sequence_variant	10/15	5		P2
BICRA	ENST00000614245.2	c.2351-2_2351del		splice_acceptor_variant, coding_sequence_variant	5/10	5		A2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 3525 AN: 123814 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.0298

Gnomad AMI AF: 0.0292

Gnomad AMR AF: 0.0209

Gnomad ASJ AF: 0.0352

Gnomad EAS AF: 0.0212

Gnomad SAS AF: 0.0204

Gnomad FIN AF: 0.0125

Gnomad MID AF: 0.00388

Gnomad NFE AF: 0.0330

Gnomad OTH AF: 0.0309

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0135 AC: 13436 AN: 996828 Hom.: 0 AF XY: 0.0149 AC XY: 7529 AN XY: 503686

Gnomad4 AFR exome AF: 0.0164

Gnomad4 AMR exome AF: 0.0438

Gnomad4 ASJ exome AF: 0.0255

Gnomad4 EAS exome AF: 0.00945

Gnomad4 SAS exome AF: 0.0383

Gnomad4 FIN exome AF: 0.0211

Gnomad4 NFE exome AF: 0.00928

Gnomad4 OTH exome AF: 0.0143

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0285 AC: 3526 AN: 123926 Hom.: 0 Cov.: 0 AF XY: 0.0265 AC XY: 1623 AN XY: 61298

Gnomad4 AFR AF: 0.0297

Gnomad4 AMR AF: 0.0208

Gnomad4 ASJ AF: 0.0352

Gnomad4 EAS AF: 0.0213

Gnomad4 SAS AF: 0.0207

Gnomad4 FIN AF: 0.0125

Gnomad4 NFE AF: 0.0330

Gnomad4 OTH AF: 0.0305

Alfa AF: 0.117 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: ExAC frequency -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.97		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.97		Position offset: 3

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

Publications

LitVar

Other links and lift over

dbSNP: rs745483989; hg19: chr19-48198619;