22-49777094-T-C

Variant names:

• chr22-49777094-T-C
• rs2059115100
• NM_001304808.3:c.3061A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001304808.3(BRD1):​c.3061A>G​(p.Ser1021Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S1021T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: BRD1 NM_001304808.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.47

Genes affected

BRD1 (HGNC:1102): (bromodomain containing 1) This gene encodes a bromodomain-containing protein that localizes to the nucleus and can interact with DNA and histone tails. The encoded protein is a component of the MOZ/MORF acetyltransferase complex and can stimulate acetylation of histones H3 and H4, thereby potentially playing a role in gene activation. Variation in this gene is associated with schizophrenia and bipolar disorder in some study populations. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 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
BRD1	NM_001304808.3	c.3061A>G	p.Ser1021Gly	missense_variant	Exon 10 of 13	ENST00000404760.6	NP_001291737.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRD1	ENST00000404760.6	c.3061A>G	p.Ser1021Gly	missense_variant	Exon 10 of 13	2	NM_001304808.3	ENSP00000385858.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 27, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2668A>G (p.S890G) alteration is located in exon 9 (coding exon 9) of the BRD1 gene. This alteration results from a A to G substitution at nucleotide position 2668, causing the serine (S) at amino acid position 890 to be replaced by a glycine (G). 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	Benign	0.11
BayesDel_addAF	Uncertain	0.051	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T;T;.;.
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	.;D;.;D
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.45	T;T;T;T
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.4	M;M;.;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.8	N;N;N;.
REVEL	Benign	0.17
Sift	Uncertain	0.0070	D;D;D;.
Sift4G	Uncertain	0.025	D;D;T;T
Polyphen		0.99	D;D;D;D
Vest4		0.43
MutPred		0.35		Gain of loop (P = 0.0195);Gain of loop (P = 0.0195);.;.;
MVP		0.67
MPC		1.1
ClinPred		0.92	D
GERP RS		5.0
Varity_R		0.32
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2059115100; hg19: chr22-50170742;