19-47679431-AG-A

Position:

• chr19-47679431-AG-A

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_001394372.1(BICRA):​c.266del​(p.Gly89AlafsTer88) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000224 in 1,336,832 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: BICRA NM_001394372.1 frameshift
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 6.16

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 Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 19-47679431-AG-A is Pathogenic according to our data. Variant chr19-47679431-AG-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3347718.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BICRA	NM_001394372.1	c.266del	p.Gly89AlafsTer88	frameshift_variant	6/15	ENST00000594866.3	NP_001381301.1
BICRA	NM_015711.3	c.266del	p.Gly89AlafsTer88	frameshift_variant	6/15		NP_056526.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BICRA	ENST00000594866.3	c.266del	p.Gly89AlafsTer88	frameshift_variant	6/15	2	NM_001394372.1	ENSP00000469738	P2
	ENST00000599924.1	n.87-52629del		intron_variant, non_coding_transcript_variant		5
BICRA	ENST00000396720.7	c.266del	p.Gly89AlafsTer88	frameshift_variant	6/15	5		ENSP00000379946	P2
BICRA	ENST00000614245.2	c.-461del		5_prime_UTR_variant	1/10	5		ENSP00000480219	A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000224 AC: 3 AN: 1336832 Hom.: 0 Cov.: 37 AF XY: 0.00000153 AC XY: 1 AN XY: 653836

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.53e-7

Gnomad4 OTH exome AF: 0.0000362

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

BICRA-related disorder Pathogenic:1

Likely pathogenic, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 24, 2024

The BICRA c.266delG variant is predicted to result in a frameshift and premature protein termination (p.Gly89Alafs*88). To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. Frameshift variants in BICRA are expected to be pathogenic. This variant is interpreted as likely pathogenic. -

Computational scores

Source: dbNSFP v4.3

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-48182688;