chr1-39764664-C-G

Position:

• chr1-39764664-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_001720.5(BMP8B):​c.827G>C​(p.Ser276Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.33 (1508 hom., cov: 38)
  • Exomes 𝑓: 0.32 (9986 hom.)
  • Failed GnomAD Quality Control
• Consequence: BMP8B NM_001720.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0550

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 (MetaRNN=0.0020771325).
• BP6: Variant 1-39764664-C-G is Benign according to our data. Variant chr1-39764664-C-G is described in ClinVar as [Benign]. Clinvar id is 767667.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMP8B	NM_001720.5	c.827G>C	p.Ser276Thr	missense_variant	4/7	ENST00000372827.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMP8B	ENST00000372827.8	c.827G>C	p.Ser276Thr	missense_variant	4/7	1	NM_001720.5	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 48130 AN: 146236 Hom.: 1510 Cov.: 38 FAILED QC

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.313

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.316 AC: 450438 AN: 1425044 Hom.: 9986 Cov.: 148 AF XY: 0.320 AC XY: 226781 AN XY: 709040

Gnomad4 AFR exome AF: 0.370

Gnomad4 AMR exome AF: 0.316

Gnomad4 ASJ exome AF: 0.323

Gnomad4 EAS exome AF: 0.369

Gnomad4 SAS exome AF: 0.444

Gnomad4 FIN exome AF: 0.288

Gnomad4 NFE exome AF: 0.303

Gnomad4 OTH exome AF: 0.327

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.329 AC: 48151 AN: 146358 Hom.: 1508 Cov.: 38 AF XY: 0.330 AC XY: 23580 AN XY: 71362

Gnomad4 AFR AF: 0.368

Gnomad4 AMR AF: 0.320

Gnomad4 ASJ AF: 0.329

Gnomad4 EAS AF: 0.350

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.282

Gnomad4 NFE AF: 0.305

Gnomad4 OTH AF: 0.313

Alfa AF: 0.241 Hom.: 89

ExAC AF: 0.340 AC: 41256

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 11, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	4.8
DANN	Benign	0.48
DEOGEN2	Benign	0.26	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0075	N
LIST_S2	Benign	0.015	T
MetaRNN	Benign	0.0021	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.1	N
MutationTaster	Benign	1.0	P;P
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.060	N
REVEL	Benign	0.041
Sift	Benign	0.83	T
Sift4G	Benign	0.61	T
Polyphen		0.0	B
Vest4		0.075
ClinPred		0.0023	T
GERP RS		0.50
Varity_R		0.033
gMVP		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: rs179472; hg19: chr1-40230336; COSMIC: COSV59593125; COSMIC: COSV59593125;