rs2071047

Variant names:

• chr14-53951693-G-A
• rs2071047
• NM_001202.6:c.370+160C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-53951693-G-A
• chr14-53951693-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_001202.6(BMP4):​c.370+160C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 1,171,306 control chromosomes in the GnomAD database, including 101,245 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (12715 hom., cov: 32)
  • Exomes 𝑓: 0.41 (88530 hom.)
• Consequence: BMP4 NM_001202.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0650
• Publications: 48 publications found

Genes affected

BMP4 (HGNC:1071): (bone morphogenetic protein 4) 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. This protein regulates heart development and adipogenesis. Mutations in this gene are associated with orofacial cleft and microphthalmia in human patients. The encoded protein may also be involved in the pathology of multiple cardiovascular diseases and human cancers. [provided by RefSeq, Jul 2016]

BMP4 Gene-Disease associations (from GenCC):

• microphthalmia with brain and digit anomalies

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: PanelApp Australia, Laboratory for Molecular Medicine, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• Stickler syndrome

  Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
• renal agenesis, unilateral

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• orofacial cleft 11

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 14-53951693-G-A is Benign according to our data. Variant chr14-53951693-G-A is described in ClinVar as Benign. ClinVar VariationId is 1167991.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP4	NM_001202.6	c.370+160C>T		intron_variant	Intron 3 of 3	ENST00000245451.9	NP_001193.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP4	ENST00000245451.9	c.370+160C>T		intron_variant	Intron 3 of 3	1	NM_001202.6	ENSP00000245451.4

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61868 AN: 151794 Hom.: 12709 Cov.: 32

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.430

GnomAD4 exome AF: 0.414 AC: 422296 AN: 1019394 Hom.: 88530 Cov.: 14 AF XY: 0.416 AC XY: 212478 AN XY: 511024

African (AFR) AF: 0.377 AC: 8909 AN: 23654

American (AMR) AF: 0.449 AC: 12597 AN: 28048

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 8512 AN: 17662

East Asian (EAS) AF: 0.490 AC: 18208 AN: 37194

South Asian (SAS) AF: 0.467 AC: 28627 AN: 61362

European-Finnish (FIN) AF: 0.372 AC: 12701 AN: 34168

Middle Eastern (MID) AF: 0.495 AC: 1505 AN: 3042

European-Non Finnish (NFE) AF: 0.406 AC: 312281 AN: 769242

Other (OTH) AF: 0.421 AC: 18956 AN: 45022

GnomAD4 genome AF: 0.408 AC: 61917 AN: 151912 Hom.: 12715 Cov.: 32 AF XY: 0.409 AC XY: 30391 AN XY: 74224

African (AFR) AF: 0.388 AC: 16084 AN: 41424

American (AMR) AF: 0.453 AC: 6913 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.486 AC: 1684 AN: 3466

East Asian (EAS) AF: 0.411 AC: 2104 AN: 5122

South Asian (SAS) AF: 0.473 AC: 2272 AN: 4808

European-Finnish (FIN) AF: 0.359 AC: 3784 AN: 10550

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.407 AC: 27630 AN: 67958

Other (OTH) AF: 0.430 AC: 910 AN: 2114

Alfa AF: 0.411 Hom.: 24242

Bravo AF: 0.411

Asia WGS AF: 0.452 AC: 1572 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 27379672) -

Microphthalmia with brain and digit anomalies;C2677434:Orofacial cleft 11 Benign:1

Dec 16, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.6
DANN	Benign	0.71
PhyloP100		0.065
PromoterAI		0.013	Neutral
Mutation Taster		=100/0	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: rs2071047; hg19: chr14-54418411; COSMIC: COSV55417383; COSMIC: COSV55417383;