1-39527206-T-G

Variant names:

• chr1-39527206-T-G
• rs1180342
• NM_181809.4:c.*1408T>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.947
• Publications: 13 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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP8A	NM_181809.4	c.*1408T>G		3_prime_UTR_variant	Exon 7 of 7	ENST00000331593.6	NP_861525.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP8A	ENST00000331593.6	c.*1408T>G		3_prime_UTR_variant	Exon 7 of 7	1	NM_181809.4	ENSP00000327440.5

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84938 AN: 151924 Hom.: 24901 Cov.: 31

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.: 31 AF XY: 0.562 AC XY: 41805 AN XY: 74334

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

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.14
CADD	Benign	14
DANN	Benign	0.81
PhyloP100		0.95

Splicing

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

Other links and lift over

dbSNP: rs1180342; hg19: chr1-39992878;