Genetic Variant BMP8A:c.*1408T>G (chr1-39527206-T-G) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4BA1

The NM_181809.4(BMP8A):c.*1408T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 152,042 control chromosomes in the GnomAD database, including 24,905 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 0.56 ( 24905 hom., cov: 31)

Consequence

BMP8A
NM_181809.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.947

Publications

13 publications found

Variant links:

Genes affected

BMP8A (HGNC:21650): (bone morphogenetic protein 8a) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. This protein may play a role in development of the reproductive system. This gene may have arose from a gene duplication event and its gene duplicate is also present on chromosome 1. [provided by RefSeq, Jul 2016]

BMP8A links:

PPIEL (HGNC:):

PPIEL links:

PPIEL (HGNC:33195): (peptidylprolyl isomerase E like (pseudogene)) This transcribed pseudogene is related to PPIE (Gene ID: 10450). Expression of this pseudogene may be downregulated in non-small cell lung cancer (NSCLC). Differential DNA methylation of this locus may be associated with intellectual disability and bipolar disorder in human patients. [provided by RefSeq, Sep 2016]

PPIEL links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.14).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181809.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BMP8A	NM_181809.4	MANE Select	c.*1408T>G	3_prime_UTR	Exon 7 of 7	NP_861525.2	Q7Z5Y6
PPIEL	NR_003929.2		n.2411+1849A>C	intron	N/A
PPIEL	NR_144354.1		n.2156+1849A>C	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BMP8A	ENST00000331593.6	TSL:1 MANE Select	c.*1408T>G	3_prime_UTR	Exon 7 of 7	ENSP00000327440.5	Q7Z5Y6
BMP8A	ENST00000970787.1		c.*1408T>G	3_prime_UTR	Exon 5 of 5	ENSP00000640846.1
PPIEL	ENST00000331856.7	TSL:2	n.1989+1849A>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.559

AC:

84938

AN:

151924

Hom.:

24901

Cov.:

show subpopulations

Gnomad AFR

AF:

0.375

Gnomad AMI

AF:

0.732

Gnomad AMR

AF:

0.597

Gnomad ASJ

AF:

0.617

Gnomad EAS

AF:

0.526

Gnomad SAS

AF:

0.768

Gnomad FIN

AF:

0.610

Gnomad MID

AF:

0.528

Gnomad NFE

AF:

0.637

Gnomad OTH

AF:

0.567

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.559

AC:

84959

AN:

152042

Hom.:

24905

Cov.:

AF XY:

0.562

AC XY:

41805

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.374

AC:

15514

AN:

41460

American (AMR)

AF:

0.598

AC:

9135

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.617

AC:

2141

AN:

3472

East Asian (EAS)

AF:

0.526

AC:

2706

AN:

5148

South Asian (SAS)

AF:

0.767

AC:

3697

AN:

4818

European-Finnish (FIN)

AF:

0.610

AC:

6454

AN:

10576

Middle Eastern (MID)

AF:

0.531

AC:

156

AN:

294

European-Non Finnish (NFE)

AF:

0.637

AC:

43296

AN:

67968

Other (OTH)

AF:

0.565

AC:

1195

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1820

3640

5461

7281

9101

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

744

1488

2232

2976

3720

<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:

0.626

Hom.:

18384

Bravo

AF:

0.543

Asia WGS

AF:

0.617

AC:

2145

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.14

CADD

Benign

(source)

DANN

Benign

0.81

PhyloP100

0.95

Splicing

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