19-47680514-C-T

Variant names:

• chr19-47680514-C-T
• rs1035938
• NM_001394372.1:c.1344C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001394372.1(BICRA):​c.1344C>T​(p.Ser448Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 1,542,428 control chromosomes in the GnomAD database, including 61,620 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 0.32 (7988 hom., cov: 32)
  • Exomes 𝑓: 0.27 (53632 hom.)
• Consequence: BICRA NM_001394372.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.840
• Publications: 21 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP7: Synonymous conserved (PhyloP=-0.84 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.425 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.1344C>T	p.Ser448Ser	synonymous	Exon 6 of 15	NP_001381301.1
	BICRA	NM_015711.3		c.1344C>T	p.Ser448Ser	synonymous	Exon 6 of 15	NP_056526.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BICRA	ENST00000594866.3	TSL:2 MANE Select	c.1344C>T	p.Ser448Ser	synonymous	Exon 6 of 15	ENSP00000469738.2
	BICRA	ENST00000396720.7	TSL:5	c.1344C>T	p.Ser448Ser	synonymous	Exon 6 of 15	ENSP00000379946.2
	BICRA	ENST00000919880.1		c.1344C>T	p.Ser448Ser	synonymous	Exon 6 of 14	ENSP00000589939.1

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47933 AN: 151748 Hom.: 7976 Cov.: 32

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.289

GnomAD2 exomes AF: 0.290 AC: 41526 AN: 143058 AF XY: 0.291

Gnomad AFR exome AF: 0.427

Gnomad AMR exome AF: 0.288

Gnomad ASJ exome AF: 0.311

Gnomad EAS exome AF: 0.290

Gnomad FIN exome AF: 0.214

Gnomad NFE exome AF: 0.271

Gnomad OTH exome AF: 0.283

GnomAD4 exome AF: 0.275 AC: 381808 AN: 1390562 Hom.: 53632 Cov.: 42 AF XY: 0.276 AC XY: 189294 AN XY: 685658

African (AFR) AF: 0.439 AC: 13793 AN: 31434

American (AMR) AF: 0.292 AC: 10204 AN: 34902

Ashkenazi Jewish (ASJ) AF: 0.314 AC: 7817 AN: 24896

East Asian (EAS) AF: 0.291 AC: 10358 AN: 35638

South Asian (SAS) AF: 0.327 AC: 25877 AN: 79130

European-Finnish (FIN) AF: 0.236 AC: 10572 AN: 44768

Middle Eastern (MID) AF: 0.300 AC: 1703 AN: 5672

European-Non Finnish (NFE) AF: 0.265 AC: 284796 AN: 1076432

Other (OTH) AF: 0.289 AC: 16688 AN: 57690

GnomAD4 genome AF: 0.316 AC: 47993 AN: 151866 Hom.: 7988 Cov.: 32 AF XY: 0.314 AC XY: 23302 AN XY: 74218

African (AFR) AF: 0.430 AC: 17825 AN: 41422

American (AMR) AF: 0.297 AC: 4540 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1057 AN: 3472

East Asian (EAS) AF: 0.292 AC: 1497 AN: 5128

South Asian (SAS) AF: 0.322 AC: 1553 AN: 4820

European-Finnish (FIN) AF: 0.222 AC: 2348 AN: 10584

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.268 AC: 18211 AN: 67856

Other (OTH) AF: 0.288 AC: 605 AN: 2104

Alfa AF: 0.291 Hom.: 11325

Bravo AF: 0.324

Asia WGS AF: 0.351 AC: 1223 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	4.4
DANN	Benign	0.84
PhyloP100		-0.84
Mutation Taster		=99/1	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: rs1035938; hg19: chr19-48183771; COSMIC: COSV67604189; COSMIC: COSV67604189;