1-39500089-A-G

Variant names:

• chr1-39500089-A-G
• rs698141
• NM_181809.4:c.334+7764A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181809.4(BMP8A):​c.334+7764A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.94 in 152,226 control chromosomes in the GnomAD database, including 67,334 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 0.94 (67334 hom., cov: 31)
• Consequence: BMP8A NM_181809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68
• Publications: 3 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 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.334+7764A>G		intron	N/A	NP_861525.2	Q7Z5Y6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP8A	ENST00000331593.6	TSL:1 MANE Select	c.334+7764A>G		intron	N/A	ENSP00000327440.5	Q7Z5Y6
	BMP8A	ENST00000970787.1		c.334+7764A>G		intron	N/A	ENSP00000640846.1

Frequencies

GnomAD3 genomes AF: 0.940 AC: 143014 AN: 152108 Hom.: 67281 Cov.: 31

Gnomad AFR AF: 0.924

Gnomad AMI AF: 0.883

Gnomad AMR AF: 0.955

Gnomad ASJ AF: 0.961

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.929

Gnomad FIN AF: 0.913

Gnomad MID AF: 0.981

Gnomad NFE AF: 0.947

Gnomad OTH AF: 0.949

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

GnomAD4 genome AF: 0.940 AC: 143126 AN: 152226 Hom.: 67334 Cov.: 31 AF XY: 0.939 AC XY: 69897 AN XY: 74416

African (AFR) AF: 0.924 AC: 38374 AN: 41528

American (AMR) AF: 0.955 AC: 14603 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.961 AC: 3335 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5175 AN: 5178

South Asian (SAS) AF: 0.929 AC: 4475 AN: 4816

European-Finnish (FIN) AF: 0.913 AC: 9676 AN: 10598

Middle Eastern (MID) AF: 0.980 AC: 288 AN: 294

European-Non Finnish (NFE) AF: 0.947 AC: 64389 AN: 68022

Other (OTH) AF: 0.949 AC: 2006 AN: 2114

Alfa AF: 0.945 Hom.: 118254

Bravo AF: 0.943

Asia WGS AF: 0.960 AC: 3339 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.082
DANN	Benign	0.34
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs698141; hg19: chr1-39965761;