rs2148328

Variant names:

• chr20-57173150-G-A
• rs2148328
• NM_001719.3:c.1146+50C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-57173150-G-A
• chr20-57173150-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001719.3(BMP7):​c.1146+50C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 1,564,692 control chromosomes in the GnomAD database, including 184,948 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (15181 hom., cov: 33)
  • Exomes 𝑓: 0.48 (169767 hom.)
• Consequence: BMP7 NM_001719.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.63
• Publications: 12 publications found

Genes affected

BMP7 (HGNC:1074): (bone morphogenetic protein 7) 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, which plays a role in bone, kidney and brown adipose tissue development. Additionally, this protein induces ectopic bone formation and may promote fracture healing in human patients. [provided by RefSeq, Jul 2016]

BMP7 Gene-Disease associations (from GenCC):

• multiple congenital anomalies/dysmorphic syndrome

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• hypospadias

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.1827637E-6).
• BP6: Variant 20-57173150-G-A is Benign according to our data. Variant chr20-57173150-G-A is described in ClinVar as Benign. ClinVar VariationId is 1242634.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001719.3. 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
	BMP7	NM_001719.3	MANE Select	c.1146+50C>T		intron	N/A	NP_001710.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP7	ENST00000395863.8	TSL:1 MANE Select	c.1146+50C>T		intron	N/A	ENSP00000379204.3
	BMP7	ENST00000450594.6	TSL:2	c.1196C>T	p.Ala399Val	missense	Exon 6 of 6	ENSP00000398687.2
	BMP7	ENST00000395864.7	TSL:5	c.948+50C>T		intron	N/A	ENSP00000379205.3

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65091 AN: 151898 Hom.: 15191 Cov.: 33

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.734

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.688

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.581

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.434

GnomAD2 exomes AF: 0.468 AC: 111568 AN: 238210 AF XY: 0.467

Gnomad AFR exome AF: 0.234

Gnomad AMR exome AF: 0.405

Gnomad ASJ exome AF: 0.425

Gnomad EAS exome AF: 0.697

Gnomad FIN exome AF: 0.590

Gnomad NFE exome AF: 0.501

Gnomad OTH exome AF: 0.465

GnomAD4 exome AF: 0.485 AC: 684705 AN: 1412676 Hom.: 169767 Cov.: 29 AF XY: 0.481 AC XY: 338766 AN XY: 704670

African (AFR) AF: 0.225 AC: 7266 AN: 32300

American (AMR) AF: 0.401 AC: 17375 AN: 43318

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 10783 AN: 25740

East Asian (EAS) AF: 0.664 AC: 26043 AN: 39196

South Asian (SAS) AF: 0.336 AC: 28401 AN: 84520

European-Finnish (FIN) AF: 0.578 AC: 30572 AN: 52866

Middle Eastern (MID) AF: 0.450 AC: 2556 AN: 5676

European-Non Finnish (NFE) AF: 0.499 AC: 534402 AN: 1070310

Other (OTH) AF: 0.465 AC: 27307 AN: 58750

GnomAD4 genome AF: 0.428 AC: 65080 AN: 152016 Hom.: 15181 Cov.: 33 AF XY: 0.432 AC XY: 32090 AN XY: 74278

African (AFR) AF: 0.238 AC: 9894 AN: 41488

American (AMR) AF: 0.422 AC: 6443 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.418 AC: 1451 AN: 3470

East Asian (EAS) AF: 0.688 AC: 3540 AN: 5146

South Asian (SAS) AF: 0.350 AC: 1683 AN: 4814

European-Finnish (FIN) AF: 0.581 AC: 6135 AN: 10552

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.504 AC: 34225 AN: 67952

Other (OTH) AF: 0.431 AC: 909 AN: 2110

Alfa AF: 0.456 Hom.: 7103

Bravo AF: 0.412

TwinsUK AF: 0.491 AC: 1822

ALSPAC AF: 0.496 AC: 1911

ESP6500AA AF: 0.249 AC: 1096

ESP6500EA AF: 0.504 AC: 4335

ExAC AF: 0.456 AC: 55264

Asia WGS AF: 0.449 AC: 1559 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.016
DANN	Benign	0.62
DEOGEN2	Benign	0.23	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.31	T
MetaRNN	Benign	0.0000032	T
MetaSVM	Benign	-1.0	T
PhyloP100		-1.6
PROVEAN	Benign	2.4	N
REVEL	Benign	0.091
Sift	Benign	0.46	T
Polyphen		0.0	B
Vest4		0.024
ClinPred		0.015	T
GERP RS		-7.7
Mutation Taster		=94/6	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: rs2148328; hg19: chr20-55748206; COSMIC: COSV67781912; COSMIC: COSV67781912;