chr1-240530702-G-A

Position:

• chr1-240530702-G-A

Variant summary

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

The NM_022469.4(GREM2):​c.-1-37226C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 152,084 control chromosomes in the GnomAD database, including 6,770 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 0.28 (6770 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: GREM2 NM_022469.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.367

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GREM2	NM_022469.4	c.-1-37226C>T		intron_variant		ENST00000318160.5	NP_071914.3
GREM2	XM_011544249.3	c.-121-33105C>T		intron_variant			XP_011542551.1
GREM2	XM_047427832.1	c.53+933C>T		intron_variant			XP_047283788.1
GREM2	XM_047427839.1	c.53+933C>T		intron_variant			XP_047283795.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GREM2	ENST00000318160.5	c.-1-37226C>T		intron_variant		1	NM_022469.4	ENSP00000318650	P1
	ENST00000457477.2	n.197G>A		non_coding_transcript_exon_variant	2/2	5

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42171 AN: 151966 Hom.: 6766 Cov.: 33

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.0840

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.265

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.278 AC: 42208 AN: 152084 Hom.: 6770 Cov.: 33 AF XY: 0.275 AC XY: 20414 AN XY: 74348

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.360

Gnomad4 ASJ AF: 0.187

Gnomad4 EAS AF: 0.0838

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.323

Gnomad4 NFE AF: 0.358

Gnomad4 OTH AF: 0.268

Alfa AF: 0.323 Hom.: 1410

Bravo AF: 0.271

Asia WGS AF: 0.183 AC: 635 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.4
DANN	Benign	0.49

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: rs3748538; hg19: chr1-240694002;