1-240542807-A-G

Position:

• chr1-240542807-A-G

Variant summary

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

The NM_022469.4(GREM2):​c.-1-49331T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 152,124 control chromosomes in the GnomAD database, including 1,286 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 0.12 (1286 hom., cov: 32)
• Consequence: GREM2 NM_022469.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.122

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GREM2	NM_022469.4	c.-1-49331T>C		intron_variant		ENST00000318160.5	NP_071914.3
GREM2	XM_011544249.3	c.-121-45210T>C		intron_variant			XP_011542551.1
GREM2	XM_047427832.1	c.-276-10844T>C		intron_variant			XP_047283788.1
GREM2	XM_047427839.1	c.-276-10844T>C		intron_variant			XP_047283795.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GREM2	ENST00000318160.5	c.-1-49331T>C		intron_variant		1	NM_022469.4	ENSP00000318650	P1

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17936 AN: 152006 Hom.: 1282 Cov.: 32

Gnomad AFR AF: 0.0623

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.126

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

GnomAD4 genome AF: 0.118 AC: 17950 AN: 152124 Hom.: 1286 Cov.: 32 AF XY: 0.118 AC XY: 8801 AN XY: 74356

Gnomad4 AFR AF: 0.0626

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.124

Alfa AF: 0.128 Hom.: 2608

Bravo AF: 0.122

Asia WGS AF: 0.157 AC: 544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.2
DANN	Benign	0.75

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: rs10495471; hg19: chr1-240706107;