1-39763082-T-C

Variant names:

• chr1-39763082-T-C
• rs138571171
• NM_001720.5:c.1059+10A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001720.5(BMP8B):​c.1059+10A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000484 in 1,612,690 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0022 (6 hom., cov: 32)
  • Exomes 𝑓: 0.00030 (3 hom.)
• Consequence: BMP8B NM_001720.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.78
• Publications: 0 publications found

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]

PPIE (HGNC:9258): (peptidylprolyl isomerase E) The protein encoded by this gene is a member of the peptidyl-prolyl cis-trans isomerase (PPIase) family. PPIases catalyze the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and accelerate the folding of proteins. This protein contains a highly conserved cyclophilin (CYP) domain as well as an RNA-binding domain. It was shown to possess PPIase and protein folding activities, and it also exhibits RNA-binding activity. Alternative splicing results in multiple transcript variants. A related pseudogene, which is also located on chromosome 1, has been identified. [provided by RefSeq, Aug 2010]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 1-39763082-T-C is Benign according to our data. Variant chr1-39763082-T-C is described in ClinVar as Benign. ClinVar VariationId is 780000.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 338 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001720.5. 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
	BMP8B	NM_001720.5	MANE Select	c.1059+10A>G		intron	N/A	NP_001711.2
	PPIE	NM_001195007.2		c.*27+431T>C		intron	N/A	NP_001181936.1	Q9UNP9-3
	PPIE	NM_203456.3		c.838-607T>C		intron	N/A	NP_982281.1	Q9UNP9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP8B	ENST00000372827.8	TSL:1 MANE Select	c.1059+10A>G		intron	N/A	ENSP00000361915.3	P34820-1
	PPIE	ENST00000372830.5	TSL:1	c.*27+431T>C		intron	N/A	ENSP00000361918.1	Q9UNP9-3
	PPIE	ENST00000356511.6	TSL:1	c.838-607T>C		intron	N/A	ENSP00000348904.2	Q9UNP9-2

Frequencies

GnomAD3 genomes AF: 0.00218 AC: 332 AN: 152034 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00701

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.000697 AC: 175 AN: 251122 AF XY: 0.000553

Gnomad AFR exome AF: 0.00837

Gnomad AMR exome AF: 0.000347

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.000490

GnomAD4 exome AF: 0.000303 AC: 442 AN: 1460540 Hom.: 3 Cov.: 31 AF XY: 0.000268 AC XY: 195 AN XY: 726676

African (AFR) AF: 0.00780 AC: 261 AN: 33442

American (AMR) AF: 0.000470 AC: 21 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39694

South Asian (SAS) AF: 0.000359 AC: 31 AN: 86234

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53400

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.0000657 AC: 73 AN: 1110826

Other (OTH) AF: 0.000795 AC: 48 AN: 60352

GnomAD4 genome AF: 0.00222 AC: 338 AN: 152150 Hom.: 6 Cov.: 32 AF XY: 0.00207 AC XY: 154 AN XY: 74384

African (AFR) AF: 0.00713 AC: 296 AN: 41512

American (AMR) AF: 0.00196 AC: 30 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5158

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 67990

Other (OTH) AF: 0.00237 AC: 5 AN: 2110

Alfa AF: 0.00148 Hom.: 0

Bravo AF: 0.00246

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.041
DANN	Benign	0.40
PhyloP100		-1.8
Mutation Taster		=100/0	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: rs138571171; hg19: chr1-40228754;