rs12129547

Variant names:

• chr1-240531955-C-T
• rs12129547
• NM_022469.4:c.-1-38479G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022469.4(GREM2):​c.-1-38479G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 151,914 control chromosomes in the GnomAD database, including 5,209 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.25 (5209 hom., cov: 31)
• Consequence: GREM2 NM_022469.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.626
• Publications: 3 publications found

Genes affected

GREM2 (HGNC:17655): (gremlin 2, DAN family BMP antagonist) This gene encodes a member of the BMP (bone morphogenic protein) antagonist family. Like BMPs, BMP antagonists contain cystine knots and typically form homo- and heterodimers. The CAN (cerberus and dan) subfamily of BMP antagonists, to which this gene belongs, is characterized by a C-terminal cystine knot with an eight-membered ring. The antagonistic effect of the secreted glycosylated protein encoded by this gene is likely due to its direct binding to BMP proteins. As an antagonist of BMP, this gene may play a role in regulating organogenesis, body patterning, and tissue differentiation. [provided by RefSeq, Jul 2008]

ENSG00000300002 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GREM2	NM_022469.4	c.-1-38479G>A		intron_variant	Intron 1 of 1	ENST00000318160.5	NP_071914.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GREM2	ENST00000318160.5	c.-1-38479G>A		intron_variant	Intron 1 of 1	1	NM_022469.4	ENSP00000318650.4
ENSG00000300002	ENST00000767897.1	n.385G>A		non_coding_transcript_exon_variant	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38589 AN: 151796 Hom.: 5215 Cov.: 31

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.245

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.259

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.254 AC: 38596 AN: 151914 Hom.: 5209 Cov.: 31 AF XY: 0.262 AC XY: 19421 AN XY: 74244

African (AFR) AF: 0.222 AC: 9208 AN: 41434

American (AMR) AF: 0.277 AC: 4219 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 852 AN: 3466

East Asian (EAS) AF: 0.519 AC: 2678 AN: 5162

South Asian (SAS) AF: 0.295 AC: 1422 AN: 4816

European-Finnish (FIN) AF: 0.310 AC: 3265 AN: 10516

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.237 AC: 16131 AN: 67948

Other (OTH) AF: 0.258 AC: 544 AN: 2110

Alfa AF: 0.246 Hom.: 18514

Bravo AF: 0.254

Asia WGS AF: 0.355 AC: 1231 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.2
DANN	Benign	0.40
PhyloP100		-0.63
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: rs12129547; hg19: chr1-240695255;