Genetic Variant NM_001394372.1:c.*53T>C (chr19-47702468-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001394372.1(BICRA):c.*53T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 1,412,996 control chromosomes in the GnomAD database, including 55,108 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.34 ( 9963 hom., cov: 32)

Exomes 𝑓: 0.26 ( 45145 hom. )

Consequence

BICRA
NM_001394372.1 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.192

Publications

23 publications found

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]

BICRA Gene-Disease associations (from GenCC):

Coffin-Siris syndrome 12
Inheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics

BICRA links:

ENSG00000268746 (HGNC:):

ENSG00000268746 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BICRA	NM_001394372.1 link	c.*53T>C		3_prime_UTR_variant	Exon 15 of 15	ENST00000594866.3	NP_001381301.1
BICRA	NM_015711.3 link	c.*53T>C		3_prime_UTR_variant	Exon 15 of 15		NP_056526.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BICRA	ENST00000594866.3 link	c.*53T>C		3_prime_UTR_variant	Exon 15 of 15	2	NM_001394372.1	ENSP00000469738.2

Frequencies

GnomAD3 genomes

AF:

0.339

AC:

51475

AN:

151908

Hom.:

9933

Cov.:

show subpopulations

Gnomad AFR

AF:

0.541

Gnomad AMI

AF:

0.255

Gnomad AMR

AF:

0.299

Gnomad ASJ

AF:

0.247

Gnomad EAS

AF:

0.345

Gnomad SAS

AF:

0.315

Gnomad FIN

AF:

0.216

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.252

Gnomad OTH

AF:

0.300

GnomAD4 exome

AF:

0.262

AC:

330099

AN:

1260972

Hom.:

45145

Cov.:

AF XY:

0.263

AC XY:

161581

AN XY:

614840

show subpopulations

African (AFR)

AF:

0.555

AC:

13492

AN:

24312

American (AMR)

AF:

0.294

AC:

3895

AN:

13244

Ashkenazi Jewish (ASJ)

AF:

0.266

AC:

5139

AN:

19312

East Asian (EAS)

AF:

0.310

AC:

8964

AN:

28882

South Asian (SAS)

AF:

0.319

AC:

19587

AN:

61420

European-Finnish (FIN)

AF:

0.243

AC:

7843

AN:

32278

Middle Eastern (MID)

AF:

0.270

AC:

992

AN:

3674

European-Non Finnish (NFE)

AF:

0.249

AC:

255460

AN:

1025402

Other (OTH)

AF:

0.281

AC:

14727

AN:

52448

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

12246

24492

36737

48983

61229

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9184

18368

27552

36736

45920

<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

AF:

0.339

AC:

51553

AN:

152024

Hom.:

9963

Cov.:

AF XY:

0.337

AC XY:

25065

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.542

AC:

22472

AN:

41478

American (AMR)

AF:

0.299

AC:

4575

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.247

AC:

856

AN:

3472

East Asian (EAS)

AF:

0.345

AC:

1771

AN:

5140

South Asian (SAS)

AF:

0.315

AC:

1515

AN:

4814

European-Finnish (FIN)

AF:

0.216

AC:

2288

AN:

10572

Middle Eastern (MID)

AF:

0.262

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.252

AC:

17135

AN:

67944

Other (OTH)

AF:

0.299

AC:

632

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1681

3362

5042

6723

8404

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

494

988

1482

1976

2470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.280

Hom.:

23691

Bravo

AF:

0.352

Asia WGS

AF:

0.358

AC:

1249

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

2.1

(source)

DANN

Benign

0.61

PhyloP100

0.19

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over