19-47673728-A-G

Position:

• chr19-47673728-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001394372.1(BICRA):​c.50A>G​(p.Gln17Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: BICRA NM_001394372.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.32

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]

ENSG00000268746 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BICRA	NM_001394372.1	c.50A>G	p.Gln17Arg	missense_variant	4/15	ENST00000594866.3	NP_001381301.1
BICRA	NM_015711.3	c.50A>G	p.Gln17Arg	missense_variant	4/15		NP_056526.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BICRA	ENST00000594866.3	c.50A>G	p.Gln17Arg	missense_variant	4/15	2	NM_001394372.1	ENSP00000469738.2
BICRA	ENST00000396720.7	c.50A>G	p.Gln17Arg	missense_variant	4/15	5		ENSP00000379946.2
ENSG00000268746	ENST00000599924.1	n.87-58337A>G		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Feb 15, 2024

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; In silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	24
DANN	Benign	0.95
DEOGEN2	Benign	0.064	T;T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Uncertain	0.087	D
MetaRNN	Uncertain	0.51	D;D
MetaSVM	Benign	-0.29	T
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.9	N;.
REVEL	Uncertain	0.41
Sift	Pathogenic	0.0	D;.
Sift4G	Uncertain	0.012	D;D
Polyphen		0.94	P;.
Vest4		0.85
MutPred		0.38		Gain of disorder (P = 0.1206);Gain of disorder (P = 0.1206);
MVP		0.71
MPC		1.2
ClinPred		0.96	D
GERP RS		3.7
Varity_R		0.25
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr19-48176985;