19-47673720-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_001394372.1(BICRA):ā€‹c.42T>Cā€‹(p.Cys14=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00017 in 1,612,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (ā˜…).

Frequency

Genomes: š‘“ 0.000086 ( 0 hom., cov: 30)
Exomes š‘“: 0.00018 ( 0 hom. )

Consequence

BICRA
NM_001394372.1 splice_region, synonymous

Scores

2
Splicing: ADA: 0.0002405
2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.84
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.32).
BP6
Variant 19-47673720-T-C is Benign according to our data. Variant chr19-47673720-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2592312.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=2.84 with no splicing effect.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0000857 (13/151660) while in subpopulation NFE AF= 0.000162 (11/67914). AF 95% confidence interval is 0.0000906. There are 0 homozygotes in gnomad4. There are 2 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
BS2
High AC in GnomAd4 at 13 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
BICRANM_001394372.1 linkuse as main transcriptc.42T>C p.Cys14= splice_region_variant, synonymous_variant 4/15 ENST00000594866.3 NP_001381301.1
BICRANM_015711.3 linkuse as main transcriptc.42T>C p.Cys14= splice_region_variant, synonymous_variant 4/15 NP_056526.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
BICRAENST00000594866.3 linkuse as main transcriptc.42T>C p.Cys14= splice_region_variant, synonymous_variant 4/152 NM_001394372.1 ENSP00000469738 P2Q9NZM4-1
ENST00000599924.1 linkuse as main transcriptn.87-58345T>C intron_variant, non_coding_transcript_variant 5
BICRAENST00000396720.7 linkuse as main transcriptc.42T>C p.Cys14= splice_region_variant, synonymous_variant 4/155 ENSP00000379946 P2Q9NZM4-1

Frequencies

GnomAD3 genomes
AF:
0.0000857
AC:
13
AN:
151660
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000657
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000162
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000189
AC:
47
AN:
248854
Hom.:
0
AF XY:
0.000177
AC XY:
24
AN XY:
135220
show subpopulations
Gnomad AFR exome
AF:
0.0000648
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000464
Gnomad NFE exome
AF:
0.000399
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000179
AC:
261
AN:
1460998
Hom.:
0
Cov.:
32
AF XY:
0.000183
AC XY:
133
AN XY:
726840
show subpopulations
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:
0.00
Gnomad4 FIN exome
AF:
0.000169
Gnomad4 NFE exome
AF:
0.000212
Gnomad4 OTH exome
AF:
0.000249
GnomAD4 genome
AF:
0.0000857
AC:
13
AN:
151660
Hom.:
0
Cov.:
30
AF XY:
0.0000270
AC XY:
2
AN XY:
74048
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.0000657
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000162
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000740
Hom.:
0
Bravo
AF:
0.0000907
EpiCase
AF:
0.000164
EpiControl
AF:
0.00

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsJul 13, 2023This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.32
CADD
Benign
15
DANN
Benign
0.92
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00024
dbscSNV1_RF
Benign
0.024
SpliceAI score (max)
0.070
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs202093781; hg19: chr19-48176977; API