rs1180341

Positions:

• chr1-39527136-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181809.4(BMP8A):​c.*1338T>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 0.486 in 151,912 control chromosomes in the GnomAD database, including 19,058 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 0.49 (19058 hom., cov: 31)
• Consequence: BMP8A NM_181809.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.274

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]

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMP8A	NM_181809.4	c.*1338T>C		3_prime_UTR_variant	7/7	ENST00000331593.6
PPIEL	NR_003929.2	n.2411+1919A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMP8A	ENST00000331593.6	c.*1338T>C		3_prime_UTR_variant	7/7	1	NM_181809.4	P1
PPIEL	ENST00000692918.1	n.1057+1919A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73854 AN: 151794 Hom.: 19060 Cov.: 31

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.682

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.518

Gnomad SAS AF: 0.749

Gnomad FIN AF: 0.519

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.492

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

GnomAD4 genome AF: 0.486 AC: 73863 AN: 151912 Hom.: 19058 Cov.: 31 AF XY: 0.492 AC XY: 36538 AN XY: 74236

Gnomad4 AFR AF: 0.310

Gnomad4 AMR AF: 0.542

Gnomad4 ASJ AF: 0.582

Gnomad4 EAS AF: 0.518

Gnomad4 SAS AF: 0.748

Gnomad4 FIN AF: 0.519

Gnomad4 NFE AF: 0.547

Gnomad4 OTH AF: 0.491

Alfa AF: 0.540 Hom.: 38565

Bravo AF: 0.472

Asia WGS AF: 0.577 AC: 2008 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.5
DANN	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1180341; hg19: chr1-39992808;