19-47696087-C-T

Variant names:

• chr19-47696087-C-T
• rs10423006
• NM_001394372.1:c.3187-364C>T

Variant summary

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

The ENST00000594866.3(BICRA):​c.3187-364C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 151,998 control chromosomes in the GnomAD database, including 3,094 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 0.20 (3094 hom., cov: 31)
• Consequence: BICRA ENST00000594866.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.28
• Publications: 3 publications found

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]

BICRA Gene-Disease associations (from GenCC):

• Coffin-Siris syndrome 12

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics

ENSG00000268746 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000594866.3. 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
	BICRA	NM_001394372.1	MANE Select	c.3187-364C>T		intron	N/A	NP_001381301.1
	BICRA	NM_015711.3		c.3187-364C>T		intron	N/A	NP_056526.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BICRA	ENST00000594866.3	TSL:2 MANE Select	c.3187-364C>T		intron	N/A	ENSP00000469738.2
	BICRA	ENST00000396720.7	TSL:5	c.3187-364C>T		intron	N/A	ENSP00000379946.2
	BICRA	ENST00000614245.2	TSL:5	c.2461-364C>T		intron	N/A	ENSP00000480219.2

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30348 AN: 151880 Hom.: 3083 Cov.: 31

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.200 AC: 30392 AN: 151998 Hom.: 3094 Cov.: 31 AF XY: 0.198 AC XY: 14727 AN XY: 74308

African (AFR) AF: 0.207 AC: 8573 AN: 41436

American (AMR) AF: 0.222 AC: 3386 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 493 AN: 3470

East Asian (EAS) AF: 0.270 AC: 1388 AN: 5144

South Asian (SAS) AF: 0.210 AC: 1012 AN: 4818

European-Finnish (FIN) AF: 0.167 AC: 1772 AN: 10596

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.194 AC: 13203 AN: 67946

Other (OTH) AF: 0.177 AC: 372 AN: 2106

Alfa AF: 0.196 Hom.: 1470

Bravo AF: 0.204

Asia WGS AF: 0.262 AC: 913 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.11
DANN	Benign	0.74
PhyloP100		-4.3
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: rs10423006; hg19: chr19-48199344;