chr1-39768569-C-T

Position:

• chr1-39768569-C-T

Variant summary

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

The NM_001720.5(BMP8B):​c.674-3752G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 148,266 control chromosomes in the GnomAD database, including 8,718 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 0.31 (8718 hom., cov: 26)
• Consequence: BMP8B NM_001720.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.356

Genes affected

BMP8B (HGNC:1075): (bone morphogenetic protein 8b) 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. The encoded protein stimulates thermogenesis in brown adipose tissue. Expression of this gene may be downregulated in pancreatic cancer. 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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMP8B	NM_001720.5	c.674-3752G>A		intron_variant		ENST00000372827.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMP8B	ENST00000372827.8	c.674-3752G>A		intron_variant		1	NM_001720.5	P1

Frequencies

GnomAD3 genomes AF: 0.314 AC: 46563 AN: 148148 Hom.: 8702 Cov.: 26

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.0968

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.320

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

GnomAD4 genome AF: 0.314 AC: 46616 AN: 148266 Hom.: 8718 Cov.: 26 AF XY: 0.309 AC XY: 22353 AN XY: 72250

Gnomad4 AFR AF: 0.455

Gnomad4 AMR AF: 0.270

Gnomad4 ASJ AF: 0.401

Gnomad4 EAS AF: 0.0970

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.250

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.315

Alfa AF: 0.131 Hom.: 204

Bravo AF: 0.330

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.51
DANN	Benign	0.40

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

Publications

LitVar

Other links and lift over

dbSNP: rs182799; hg19: chr1-40234241;