rs1035938

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr19-47680514-C-G
• chr19-47680514-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001394372.1(BICRA):​c.1344C>G​(p.Ser448Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S448I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BICRA NM_001394372.1 missense
• 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: Uncertain_significance. The variant received 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BICRA	NM_001394372.1	c.1344C>G	p.Ser448Arg	missense_variant	Exon 6 of 15	ENST00000594866.3	NP_001381301.1
BICRA	NM_015711.3	c.1344C>G	p.Ser448Arg	missense_variant	Exon 6 of 15		NP_056526.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BICRA	ENST00000594866.3	c.1344C>G	p.Ser448Arg	missense_variant	Exon 6 of 15	2	NM_001394372.1	ENSP00000469738.2
BICRA	ENST00000396720.7	c.1344C>G	p.Ser448Arg	missense_variant	Exon 6 of 15	5		ENSP00000379946.2
BICRA	ENST00000614245.2	c.618C>G	p.Ser206Arg	missense_variant	Exon 1 of 10	5		ENSP00000480219.2
ENSG00000268746	ENST00000599924.1	n.87-51551C>G		intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 42

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 11325

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.090
CADD	Benign	13
DANN	Benign	0.87
DEOGEN2	Benign	0.064	T;.
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.84	T;T
M_CAP	Benign	0.077	D
MetaRNN	Uncertain	0.59	D;D
MetaSVM	Benign	-0.45	T
PhyloP100		-0.84
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-2.1	N;.
REVEL	Uncertain	0.33
Sift	Uncertain	0.0010	D;.
Sift4G	Benign	0.061	T;T
Polyphen		1.0	D;.
Vest4		0.77
MutPred		0.35		Loss of loop (P = 0.0022);.;
MVP		0.57
MPC		0.21
ClinPred		0.49	T
GERP RS		-2.1
Varity_R		0.29
gMVP		0.78
Mutation Taster		=43/57	disease causing

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;