Genetic Variant BRAFP1:n.1918G>T (chrX-75584721-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000445336.2(BRAFP1):n.1918G>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000381 in 1,050,124 control chromosomes in the GnomAD database, including 1 homozygotes. There are no hemizygote samples in GnomAD. 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 0.0000089 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.0000032 ( 1 hom. 0 hem. )

Consequence

BRAFP1
ENST00000445336.2 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.62

Publications

1 publications found

Variant links:

Genes affected

BRAFP1 (HGNC:18615): (BRAF pseudogene 1)

BRAFP1 links:

ENSG00000302260 (HGNC:):

ENSG00000302260 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
BRAFP1		n.75584721G>T	intragenic_variant
LOC107985664	XR_001755885.2 link	n.529-20197G>T	intron_variant	Intron 1 of 3
LOC107985664	XR_001755889.2 link	n.646+4983G>T	intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
BRAFP1	ENST00000445336.2 link	n.1918G>T	non_coding_transcript_exon_variant	Exon 2 of 2	6
ENSG00000302260	ENST00000785233.1 link	n.419-20197G>T	intron_variant	Intron 1 of 5
ENSG00000302260	ENST00000785234.1 link	n.125-20197G>T	intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.00000894

AC:

AN:

111911

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000320

AC:

AN:

938213

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

293443

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

23226

American (AMR)

AF:

0.00

AC:

AN:

34910

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18407

East Asian (EAS)

AF:

0.00

AC:

AN:

29445

South Asian (SAS)

AF:

0.00

AC:

AN:

50604

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40171

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2604

European-Non Finnish (NFE)

AF:

0.00000143

AC:

AN:

698237

Other (OTH)

AF:

0.0000493

AC:

AN:

40609

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

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

AF:

0.00000894

AC:

AN:

111911

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34073

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30785

American (AMR)

AF:

0.00

AC:

AN:

10577

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2640

East Asian (EAS)

AF:

0.00

AC:

AN:

3577

South Asian (SAS)

AF:

0.00

AC:

AN:

2651

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6025

Middle Eastern (MID)

AF:

0.00

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53224

Other (OTH)

AF:

0.00

AC:

AN:

1510

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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

1.0

(source)

DANN

Benign

0.35

PhyloP100

2.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over