chr1-39492001-C-A

Variant names:

• chr1-39492001-C-A
• rs1192579480
• NM_181809.4:c.10C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_181809.4(BMP8A):​c.10C>A​(p.Arg4Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000321 in 934,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000032 (0 hom.)
• Consequence: BMP8A NM_181809.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.143
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15153182).

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.10C>A	p.Arg4Ser	missense	Exon 1 of 7	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.10C>A	p.Arg4Ser	missense	Exon 1 of 7	ENSP00000327440.5	Q7Z5Y6
	BMP8A	ENST00000970787.1		c.10C>A	p.Arg4Ser	missense	Exon 1 of 5	ENSP00000640846.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000321 AC: 3 AN: 934686 Hom.: 0 Cov.: 28 AF XY: 0.00000456 AC XY: 2 AN XY: 438246

African (AFR) AF: 0.00 AC: 0 AN: 18084

American (AMR) AF: 0.000499 AC: 2 AN: 4008

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8256

East Asian (EAS) AF: 0.00 AC: 0 AN: 11256

South Asian (SAS) AF: 0.00 AC: 0 AN: 18214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 11542

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2130

European-Non Finnish (NFE) AF: 0.00000121 AC: 1 AN: 827770

Other (OTH) AF: 0.00 AC: 0 AN: 33426

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	15
DANN	Benign	0.85
DEOGEN2	Benign	0.072	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.36	T
M_CAP	Pathogenic	0.44	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.20	N
PhyloP100		0.14
PrimateAI	Pathogenic	0.80	D
PROVEAN	Benign	-0.23	N
REVEL	Benign	0.14
Sift	Benign	0.069	T
Sift4G	Uncertain	0.033	D
Polyphen		0.010	B
Vest4		0.18
MutPred		0.30		Loss of methylation at R4 (P = 0.0062)
MVP		0.61
MPC		1.6
ClinPred		0.11	T
GERP RS		3.1
PromoterAI		0.030	Neutral
Varity_R		0.13
gMVP		0.59
Mutation Taster		=88/12	polymorphism

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: rs1192579480; hg19: chr1-39957673;