19-47702468-T-C

Variant names:

• chr19-47702468-T-C
• rs3745760
• NM_001394372.1:c.*53T>C

Variant summary

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

The NM_001394372.1(BICRA):​c.*53T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 1,412,996 control chromosomes in the GnomAD database, including 55,108 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 0.34 (9963 hom., cov: 32)
  • Exomes 𝑓: 0.26 (45145 hom.)
• Consequence: BICRA NM_001394372.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.192
• Publications: 23 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

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394372.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BICRA	NM_001394372.1	MANE Select	c.*53T>C		3_prime_UTR	Exon 15 of 15	NP_001381301.1	Q9NZM4-1
	BICRA	NM_015711.3		c.*53T>C		3_prime_UTR	Exon 15 of 15	NP_056526.3	Q9NZM4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BICRA	ENST00000594866.3	TSL:2 MANE Select	c.*53T>C		3_prime_UTR	Exon 15 of 15	ENSP00000469738.2	Q9NZM4-1
	BICRA	ENST00000396720.7	TSL:5	c.*53T>C		3_prime_UTR	Exon 15 of 15	ENSP00000379946.2	Q9NZM4-1
	BICRA	ENST00000919880.1		c.*53T>C		3_prime_UTR	Exon 14 of 14	ENSP00000589939.1

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51475 AN: 151908 Hom.: 9933 Cov.: 32

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.345

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.300

GnomAD4 exome AF: 0.262 AC: 330099 AN: 1260972 Hom.: 45145 Cov.: 31 AF XY: 0.263 AC XY: 161581 AN XY: 614840

African (AFR) AF: 0.555 AC: 13492 AN: 24312

American (AMR) AF: 0.294 AC: 3895 AN: 13244

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 5139 AN: 19312

East Asian (EAS) AF: 0.310 AC: 8964 AN: 28882

South Asian (SAS) AF: 0.319 AC: 19587 AN: 61420

European-Finnish (FIN) AF: 0.243 AC: 7843 AN: 32278

Middle Eastern (MID) AF: 0.270 AC: 992 AN: 3674

European-Non Finnish (NFE) AF: 0.249 AC: 255460 AN: 1025402

Other (OTH) AF: 0.281 AC: 14727 AN: 52448

GnomAD4 genome AF: 0.339 AC: 51553 AN: 152024 Hom.: 9963 Cov.: 32 AF XY: 0.337 AC XY: 25065 AN XY: 74294

African (AFR) AF: 0.542 AC: 22472 AN: 41478

American (AMR) AF: 0.299 AC: 4575 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 856 AN: 3472

East Asian (EAS) AF: 0.345 AC: 1771 AN: 5140

South Asian (SAS) AF: 0.315 AC: 1515 AN: 4814

European-Finnish (FIN) AF: 0.216 AC: 2288 AN: 10572

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.252 AC: 17135 AN: 67944

Other (OTH) AF: 0.299 AC: 632 AN: 2112

Alfa AF: 0.280 Hom.: 23691

Bravo AF: 0.352

Asia WGS AF: 0.358 AC: 1249 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.1
DANN	Benign	0.61
PhyloP100		0.19
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: rs3745760; hg19: chr19-48205725;