rs1180341

Variant names:

• chr1-39527136-T-C
• rs1180341
• NM_181809.4:c.*1338T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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:):

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

Our verdict: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP8A	NM_181809.4	MANE Select	c.*1338T>C		3_prime_UTR	Exon 7 of 7	NP_861525.2	Q7Z5Y6
	PPIEL	NR_003929.2		n.2411+1919A>G		intron	N/A
	PPIEL	NR_144354.1		n.2156+1919A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP8A	ENST00000331593.6	TSL:1 MANE Select	c.*1338T>C		3_prime_UTR	Exon 7 of 7	ENSP00000327440.5	Q7Z5Y6
	BMP8A	ENST00000970787.1		c.*1338T>C		3_prime_UTR	Exon 5 of 5	ENSP00000640846.1
	PPIEL	ENST00000331856.7	TSL:2	n.1989+1919A>G		intron	N/A

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

African (AFR) AF: 0.310 AC: 12859 AN: 41424

American (AMR) AF: 0.542 AC: 8276 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.582 AC: 2019 AN: 3468

East Asian (EAS) AF: 0.518 AC: 2664 AN: 5144

South Asian (SAS) AF: 0.748 AC: 3607 AN: 4820

European-Finnish (FIN) AF: 0.519 AC: 5461 AN: 10530

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.547 AC: 37184 AN: 67940

Other (OTH) AF: 0.491 AC: 1035 AN: 2108

Alfa AF: 0.526 Hom.: 59593

Bravo AF: 0.472

Asia WGS AF: 0.577 AC: 2008 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.5
DANN	Benign	0.75
PhyloP100		-0.27

Splicing

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

Other links and lift over

dbSNP: rs1180341; hg19: chr1-39992808;