19-47679421-C-G

Position:

• chr19-47679421-C-G

Variant summary

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

The NM_001394372.1(BICRA):​c.251C>G​(p.Ser84Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000015 in 1,333,950 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: BICRA NM_001394372.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.59

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31323627).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BICRA	NM_001394372.1	c.251C>G	p.Ser84Cys	missense_variant	6/15	ENST00000594866.3
BICRA	NM_015711.3	c.251C>G	p.Ser84Cys	missense_variant	6/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BICRA	ENST00000594866.3	c.251C>G	p.Ser84Cys	missense_variant	6/15	2	NM_001394372.1	P2
	ENST00000599924.1	n.87-52644C>G		intron_variant, non_coding_transcript_variant		5
BICRA	ENST00000396720.7	c.251C>G	p.Ser84Cys	missense_variant	6/15	5		P2
BICRA	ENST00000614245.2	c.-476C>G		5_prime_UTR_variant	1/10	5		A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000150 AC: 2 AN: 1333950 Hom.: 0 Cov.: 36 AF XY: 0.00000307 AC XY: 2 AN XY: 652022

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000145

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.54e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 14, 2023

The c.251C>G (p.S84C) alteration is located in exon 6 (coding exon 4) of the GLTSCR1 gene. This alteration results from a C to G substitution at nucleotide position 251, causing the serine (S) at amino acid position 84 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	24
DANN	Benign	0.78
DEOGEN2	Benign	0.089	T;T;.
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.78	T;T;T
M_CAP	Pathogenic	0.32	D
MetaRNN	Benign	0.31	T;T;T
MetaSVM	Uncertain	-0.14	T
MutationTaster	Benign	0.99	D
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-2.6	D;.;.
REVEL	Benign	0.17
Sift	Uncertain	0.0010	D;.;.
Sift4G	Uncertain	0.0050	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.57
MutPred		0.19		Loss of glycosylation at S84 (P = 0.0108);Loss of glycosylation at S84 (P = 0.0108);.;
MVP		0.24
MPC		1.1
ClinPred		0.65	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.24
gMVP		0.48

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: chr19-48182678;