19-47679507-A-G

Position:

• chr19-47679507-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001394372.1(BICRA):​c.337A>G​(p.Ile113Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: BICRA NM_001394372.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.95

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21834761).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BICRA	NM_001394372.1	c.337A>G	p.Ile113Val	missense_variant	6/15	ENST00000594866.3	NP_001381301.1
BICRA	NM_015711.3	c.337A>G	p.Ile113Val	missense_variant	6/15		NP_056526.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BICRA	ENST00000594866.3	c.337A>G	p.Ile113Val	missense_variant	6/15	2	NM_001394372.1	ENSP00000469738	P2
	ENST00000599924.1	n.87-52558A>G		intron_variant, non_coding_transcript_variant		5
BICRA	ENST00000396720.7	c.337A>G	p.Ile113Val	missense_variant	6/15	5		ENSP00000379946	P2
BICRA	ENST00000614245.2	c.-390A>G		5_prime_UTR_variant	1/10	5		ENSP00000480219	A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 33

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

Mar 16, 2023

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; 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	0.97
BayesDel_addAF	Uncertain	0.037	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	23
DANN	Benign	0.88
DEOGEN2	Benign	0.19	T;T;.
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D;D;D
M_CAP	Benign	0.074	D
MetaRNN	Benign	0.22	T;T;T
MetaSVM	Uncertain	-0.20	T
MutationTaster	Benign	0.83	D
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.26	N;.;.
REVEL	Benign	0.28
Sift	Uncertain	0.0060	D;.;.
Sift4G	Benign	0.28	T;D;T
Polyphen		0.99	D;.;.
Vest4		0.42
MutPred		0.096		Loss of catalytic residue at L118 (P = 0.0969);Loss of catalytic residue at L118 (P = 0.0969);.;
MVP		0.40
MPC		0.99
ClinPred		0.48	T
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.078
gMVP		0.32

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: chr19-48182764;