chr20-57233824-G-A

Variant names:

• chr20-57233824-G-A
• rs162315
• NM_001719.3:c.419-5403C>T

GermlineCancer (beta)

Variant summary

Our verdict is Benign.

<-10 Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_Strong

The NM_001719.3(BMP7):c.419-5403C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.381 (AC=58,003) in the gnomAD database across 152,170 control chromosomes, including 14,683 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.716. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.38 (14683 hom., cov: 33)
• Consequence: BMP7 NM_001719.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.307
• Publications: 5 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
• congenital anomaly of kidney and urinary tract

  Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia
• hypospadias

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• isolated craniosynostosis

  Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia
• Mayer-Rokitansky-Kuster-Hauser syndrome

  Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Benign. The variant received -12 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).
	BA1Stand-alone benign allele frequency (>5%)		GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.7155 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_001719.3. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	BMP7 NM_001719.3	MANE Select	c.419-5403C>T	intron	Intron 1 of 6	Prot: NP_001710.1 UniProt:

BMP7 NM_001719.3

MANE Select

HGVSc / HGVSpc.419-5403C>T

Exon rankIntron 1 of 6

intron

Prot: NP_001710.1UniProt: P18075A8K571

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	BMP7 ENST00000395863.8	TSL:1MANE Select	c.419-5403C>T	intron	Intron 1 of 6	Prot: ENSP00000379204.3 UniProt:
	BMP7 ENST00000450594.6	TSL:2	c.419-5403C>T	intron	Intron 1 of 5	Prot: ENSP00000398687.2 UniProt:
	BMP7 ENST00000395864.7	TSL:5	c.419-5403C>T	intron	Intron 1 of 5	Prot: ENSP00000379205.3 UniProt:

BMP7 ENST00000395863.8

TSL:1MANE Select

HGVSc / HGVSpc.419-5403C>T

Exon rankIntron 1 of 6

intron

Prot: ENSP00000379204.3UniProt: P18075

BMP7 ENST00000450594.6

TSL:2

HGVSc / HGVSpc.419-5403C>T

Exon rankIntron 1 of 5

intron

Prot: ENSP00000398687.2UniProt: B1AL00

BMP7 ENST00000395864.7

TSL:5

HGVSc / HGVSpc.419-5403C>T

Exon rankIntron 1 of 5

intron

Prot: ENSP00000379205.3UniProt: B1AKZ9

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 4 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.381	AC:57917	Hom:14661	AN:152052	Cov:33
GnomAD4 genome	AF: 0.381	AC:58003	Hom:14683	AN:152170	Cov:33
TOPMed (Bravo)	AF: 0.412	AC:109069	Hom:28503	AN:264690	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.292	AC:29138	Hom:5580	AN:99958	Cov:
Local & regional cohorts 10 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.392	AC:918	Hom:201	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.320	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.180	AC:54	Hom:	AN:300	Cov:
GenomeAsia100K	AF: 0.340	AC:1182	Hom:	AN:3478	Cov:
Korea4K (4,157 Koreans)	AF: 0.248	AC:1796	Hom:	AN:7232	Cov:
Qatari Genome	AF: 0.364	AC:64	Hom:	AN:176	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.229	AC:28065	Hom:3227	AN:122818	Cov:
Turkish Variome	AF: 0.223	AC:344	Hom:35	AN:1546	Cov:
UK10K	AF: 0.239	AC:1804	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.340	AC:3050	Hom:527	AN:8960	Cov:

Showing 14 sources

Tested, but no data found:GnomAD4 exomeIf GnomAD4 is missing, the position is probably not covered by the project.

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	0.62
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.9
DANN	Benign	0.75
GPN-Star LLR	N/A	-1.4
GPN-Star score	N/A	1.4
Mutation Taster	N/A	100/0	polymorphism (auto)
PhyloP100	Benign	-0.31

Showing 8 of 8 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs162315;

hg19: chr20-55808880;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar