19-47679362-G-C

Position:

• chr19-47679362-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP5 BP4

The NM_001394372.1(BICRA):​c.192G>C​(p.Glu64Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: BICRA NM_001394372.1 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 2.42

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 19-47679362-G-C is Pathogenic according to our data. Variant chr19-47679362-G-C is described in ClinVar as [Pathogenic]. Clinvar id is 1106681.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr19-47679362-G-C is described in Lovd as [Likely_pathogenic].
• BP4: Computational evidence support a benign effect (MetaRNN=0.21524936). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BICRA	NM_001394372.1	c.192G>C	p.Glu64Asp	missense_variant	6/15	ENST00000594866.3
BICRA	NM_015711.3	c.192G>C	p.Glu64Asp	missense_variant	6/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BICRA	ENST00000594866.3	c.192G>C	p.Glu64Asp	missense_variant	6/15	2	NM_001394372.1	P2
	ENST00000599924.1	n.87-52703G>C		intron_variant, non_coding_transcript_variant		5
BICRA	ENST00000396720.7	c.192G>C	p.Glu64Asp	missense_variant	6/15	5		P2
BICRA	ENST00000614245.2	c.-535G>C		5_prime_UTR_variant	1/10	5		A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Coffin-Siris syndrome 12 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

May 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	20
DANN	Benign	0.94
DEOGEN2	Benign	0.013	T;T;.
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.75	T;T;T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.22	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.4	N;.;.
REVEL	Benign	0.14
Sift	Benign	0.16	T;.;.
Sift4G	Benign	0.39	T;T;T
Polyphen		1.0	D;.;.
Vest4		0.16
MutPred		0.086		Loss of glycosylation at P65 (P = 0.1454);Loss of glycosylation at P65 (P = 0.1454);.;
MVP		0.45
MPC		1.1
ClinPred		0.45	T
GERP RS		4.9
Varity_R		0.14
gMVP		0.063

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: chr19-48182619;