19-15238734-C-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001379291.1(BRD4):c.4020+9G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00571 in 1,525,150 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0037 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0059 (38 hom.)
• Consequence: BRD4 NM_001379291.1 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.553

Genes affected

BRD4 (HGNC:13575): (bromodomain containing 4) The protein encoded by this gene is homologous to the murine protein MCAP, which associates with chromosomes during mitosis, and to the human RING3 protein, a serine/threonine kinase. Each of these proteins contains two bromodomains, a conserved sequence motif which may be involved in chromatin targeting. This gene has been implicated as the chromosome 19 target of translocation t(15;19)(q13;p13.1), which defines an upper respiratory tract carcinoma in young people. Two alternatively spliced transcript variants have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 19-15238734-C-A is Benign according to our data. Variant chr19-15238734-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 778171.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd at 564 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRD4	NM_001379291.1	c.4020+9G>T		intron_variant		ENST00000679869.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRD4	ENST00000679869.1	c.4020+9G>T		intron_variant			NM_001379291.1	P1
BRD4	ENST00000263377.6	c.4020+9G>T		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.00370 AC: 564 AN: 152250 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00116

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.00412

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00613

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00355 AC: 597 AN: 168248 Hom.: 1 AF XY: 0.00337 AC XY: 303 AN XY: 89832

Gnomad AFR exome AF: 0.000832

Gnomad AMR exome AF: 0.00264

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000959

Gnomad FIN exome AF: 0.00129

Gnomad NFE exome AF: 0.00620

Gnomad OTH exome AF: 0.00546

GnomAD4 exome AF: 0.00593 AC: 8143 AN: 1372782 Hom.: 38 Cov.: 32 AF XY: 0.00577 AC XY: 3880 AN XY: 672534

Gnomad4 AFR exome AF: 0.000832

Gnomad4 AMR exome AF: 0.00296

Gnomad4 ASJ exome AF: 0.000142

Gnomad4 EAS exome AF: 0.0000262

Gnomad4 SAS exome AF: 0.00106

Gnomad4 FIN exome AF: 0.00157

Gnomad4 NFE exome AF: 0.00712

Gnomad4 OTH exome AF: 0.00458

GnomAD4 genome AF: 0.00371 AC: 565 AN: 152368 Hom.: 3 Cov.: 32 AF XY: 0.00329 AC XY: 245 AN XY: 74506

Gnomad4 AFR AF: 0.00115

Gnomad4 AMR AF: 0.00411

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.000565

Gnomad4 NFE AF: 0.00613

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00385 Hom.: 2

Bravo AF: 0.00400

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

BRD4-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 12, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	2.0
Dann	Benign	0.80

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

LitVar

Other links and lift over

dbSNP: rs200578182; hg19: chr19-15349545;