Genetic Variant BRD1:p.Ser1183Arg (chr22-49774254-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001304808.3(BRD1):c.3549C>G(p.Ser1183Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,500 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S1183S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

BRD1
NM_001304808.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0710

Publications

0 publications found

Variant links:

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]

BRD1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17870608).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001304808.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BRD1	NM_001304808.3	MANE Select	c.3549C>G	p.Ser1183Arg	missense	Exon 13 of 13	NP_001291737.1	O95696-2
BRD1	NM_001394548.1		c.3543C>G	p.Ser1181Arg	missense	Exon 13 of 13	NP_001381477.1
BRD1	NM_001349941.2		c.3534C>G	p.Ser1178Arg	missense	Exon 13 of 13	NP_001336870.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BRD1	ENST00000404760.6	TSL:2 MANE Select	c.3549C>G	p.Ser1183Arg	missense	Exon 13 of 13	ENSP00000385858.1	O95696-2
BRD1	ENST00000216267.12	TSL:1	c.3156C>G	p.Ser1052Arg	missense	Exon 12 of 12	ENSP00000216267.8	O95696-1
BRD1	ENST00000404034.5	TSL:1	c.3156C>G	p.Ser1052Arg	missense	Exon 13 of 13	ENSP00000384076.1	O95696-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461500

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726990

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33468

American (AMR)

AF:

0.00

AC:

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39684

South Asian (SAS)

AF:

0.00

AC:

AN:

86240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53354

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111802

Other (OTH)

AF:

0.00

AC:

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.68

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.18

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.79

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.94

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.66

MutationAssessor

Benign

1.8

PhyloP100

-0.071

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.18

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0040

Polyphen

0.0080

Vest4

0.36

MutPred

0.15

Loss of phosphorylation at S1052 (P = 0.0502)

MVP

0.36

MPC

1.3

ClinPred

0.98

GERP RS

-8.6

Varity_R

0.58

gMVP

0.48

Mutation Taster

=71/29

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over