19-47679311-C-T

Position:

• chr19-47679311-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001394372.1(BICRA):​c.151-10C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.754 in 1,419,060 control chromosomes in the GnomAD database, including 405,848 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.80 (49599 hom., cov: 33)
  • Exomes 𝑓: 0.75 (356249 hom.)
• Consequence: BICRA NM_001394372.1 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00002816
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.89

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 19-47679311-C-T is Benign according to our data. Variant chr19-47679311-C-T is described in ClinVar as [Benign]. Clinvar id is 1342756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.937 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BICRA	NM_001394372.1	c.151-10C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000594866.3
BICRA	NM_015711.3	c.151-10C>T		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BICRA	ENST00000594866.3	c.151-10C>T		splice_polypyrimidine_tract_variant, intron_variant		2	NM_001394372.1	P2
	ENST00000599924.1	n.87-52754C>T		intron_variant, non_coding_transcript_variant		5
BICRA	ENST00000614245.2	c.-586C>T		5_prime_UTR_variant	1/10	5		A2
BICRA	ENST00000396720.7	c.151-10C>T		splice_polypyrimidine_tract_variant, intron_variant		5		P2

Frequencies

GnomAD3 genomes AF: 0.802 AC: 121953 AN: 152068 Hom.: 49527 Cov.: 33

Gnomad AFR AF: 0.909

Gnomad AMI AF: 0.858

Gnomad AMR AF: 0.808

Gnomad ASJ AF: 0.692

Gnomad EAS AF: 0.960

Gnomad SAS AF: 0.818

Gnomad FIN AF: 0.788

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.730

Gnomad OTH AF: 0.768

GnomAD3 exomes AF: 0.773 AC: 43580 AN: 56414 Hom.: 17053 AF XY: 0.769 AC XY: 21590 AN XY: 28086

Gnomad AFR exome AF: 0.907

Gnomad AMR exome AF: 0.810

Gnomad ASJ exome AF: 0.684

Gnomad EAS exome AF: 0.956

Gnomad SAS exome AF: 0.778

Gnomad FIN exome AF: 0.766

Gnomad NFE exome AF: 0.713

Gnomad OTH exome AF: 0.763

GnomAD4 exome AF: 0.748 AC: 947626 AN: 1266874 Hom.: 356249 Cov.: 34 AF XY: 0.749 AC XY: 458701 AN XY: 612042

Gnomad4 AFR exome AF: 0.923

Gnomad4 AMR exome AF: 0.821

Gnomad4 ASJ exome AF: 0.696

Gnomad4 EAS exome AF: 0.964

Gnomad4 SAS exome AF: 0.815

Gnomad4 FIN exome AF: 0.780

Gnomad4 NFE exome AF: 0.730

Gnomad4 OTH exome AF: 0.770

GnomAD4 genome AF: 0.802 AC: 122086 AN: 152186 Hom.: 49599 Cov.: 33 AF XY: 0.806 AC XY: 59967 AN XY: 74400

Gnomad4 AFR AF: 0.910

Gnomad4 AMR AF: 0.809

Gnomad4 ASJ AF: 0.692

Gnomad4 EAS AF: 0.960

Gnomad4 SAS AF: 0.818

Gnomad4 FIN AF: 0.788

Gnomad4 NFE AF: 0.730

Gnomad4 OTH AF: 0.770

Alfa AF: 0.742 Hom.: 57046

Bravo AF: 0.809

Asia WGS AF: 0.887 AC: 3088 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 24, 2022	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.082
DANN	Benign	0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000028
dbscSNV1_RF	Benign	0.026
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

LitVar

Other links and lift over

dbSNP: rs2911005; hg19: chr19-48182568;