1-240509503-T-G

Variant names:

• chr1-240509503-T-G
• rs61832588
• NM_022469.4:c.-1-16027A>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_022469.4(GREM2):​c.-1-16027A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 151,698 control chromosomes in the GnomAD database, including 1,905 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.14 (1905 hom., cov: 29)
• Consequence: GREM2 NM_022469.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.841
• Publications: 0 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]

GREM2 Gene-Disease associations (from GenCC):

• tooth agenesis, selective, 9

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 1-240509503-T-G is Benign according to our data. Variant chr1-240509503-T-G is described in ClinVar as Benign. ClinVar VariationId is 873242.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022469.4. 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
	GREM2	NM_022469.4	MANE Select	c.-1-16027A>C		intron	N/A	NP_071914.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GREM2	ENST00000318160.5	TSL:1 MANE Select	c.-1-16027A>C		intron	N/A	ENSP00000318650.4	Q9H772
	GREM2	ENST00000859904.1		c.-121-11906A>C		intron	N/A	ENSP00000529963.1
	GREM2	ENST00000942417.1		c.-1-16027A>C		intron	N/A	ENSP00000612476.1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21853 AN: 151582 Hom.: 1897 Cov.: 29

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.000585

Gnomad SAS AF: 0.0162

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.128

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.144 AC: 21904 AN: 151698 Hom.: 1905 Cov.: 29 AF XY: 0.143 AC XY: 10613 AN XY: 74162

African (AFR) AF: 0.237 AC: 9810 AN: 41318

American (AMR) AF: 0.112 AC: 1702 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 422 AN: 3468

East Asian (EAS) AF: 0.000586 AC: 3 AN: 5118

South Asian (SAS) AF: 0.0165 AC: 79 AN: 4802

European-Finnish (FIN) AF: 0.143 AC: 1512 AN: 10552

Middle Eastern (MID) AF: 0.128 AC: 37 AN: 290

European-Non Finnish (NFE) AF: 0.116 AC: 7889 AN: 67934

Other (OTH) AF: 0.151 AC: 317 AN: 2106

Alfa AF: 0.0409 Hom.: 33

Bravo AF: 0.148

Asia WGS AF: 0.0300 AC: 103 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.59
PhyloP100		-0.84
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: rs61832588; hg19: chr1-240672803;