chr1-240553161-C-A

Position:

• chr1-240553161-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022469.4(GREM2):​c.-2+58723G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,100 control chromosomes in the GnomAD database, including 2,660 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 0.16 (2660 hom., cov: 33)
• Consequence: GREM2 NM_022469.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.236

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GREM2	NM_022469.4	c.-2+58723G>T		intron_variant		ENST00000318160.5	NP_071914.3
GREM2	XM_047427832.1	c.-276-21198G>T		intron_variant			XP_047283788.1
GREM2	XM_047427839.1	c.-277+17732G>T		intron_variant			XP_047283795.1
GREM2	XM_011544249.3	c.-121-55564G>T		intron_variant			XP_011542551.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GREM2	ENST00000318160.5	c.-2+58723G>T		intron_variant		1	NM_022469.4	ENSP00000318650.4

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23759 AN: 151982 Hom.: 2648 Cov.: 33

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.0982

Gnomad EAS AF: 0.0844

Gnomad SAS AF: 0.0601

Gnomad FIN AF: 0.0682

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0942

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.157 AC: 23809 AN: 152100 Hom.: 2660 Cov.: 33 AF XY: 0.153 AC XY: 11414 AN XY: 74370

Gnomad4 AFR AF: 0.313

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.0982

Gnomad4 EAS AF: 0.0848

Gnomad4 SAS AF: 0.0604

Gnomad4 FIN AF: 0.0682

Gnomad4 NFE AF: 0.0942

Gnomad4 OTH AF: 0.143

Alfa AF: 0.125 Hom.: 398

Bravo AF: 0.174

Asia WGS AF: 0.0790 AC: 275 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	14
DANN	Benign	0.86

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

Publications

LitVar

Other links and lift over

dbSNP: rs7411138; hg19: chr1-240716461;