ENST00000908783.1:c.-2+263C>G

Variant names:

• chr15-32717373-C-G
• rs1919364
• ENST00000908783.1:c.-2+263C>G

Variant summary

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

The ENST00000908783.1(GREM1):​c.-2+263C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 152,036 control chromosomes in the GnomAD database, including 31,502 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 0.62 (31494 hom., cov: 31)
  • Exomes 𝑓: 0.58 (8 hom.)
• Consequence: GREM1 ENST00000908783.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.406
• Publications: 13 publications found

Genes affected

GREM1 (HGNC:2001): (gremlin 1, 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. In mouse, this protein has been shown to relay the sonic hedgehog (SHH) signal from the polarizing region to the apical ectodermal ridge during limb bud outgrowth. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2010]

GREM1-AS1 (HGNC:55411): (GREM1 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.936 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000908783.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GREM1	ENST00000908783.1		c.-2+263C>G		intron	N/A	ENSP00000578842.1
	GREM1-AS1	ENST00000558441.1	TSL:6	n.1635G>C		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.625 AC: 94853 AN: 151880 Hom.: 31453 Cov.: 31

Gnomad AFR AF: 0.818

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.588

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.958

Gnomad SAS AF: 0.757

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.548

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.589

GnomAD4 exome AF: 0.579 AC: 22 AN: 38 Hom.: 8 Cov.: 0 AF XY: 0.577 AC XY: 15 AN XY: 26

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AF: 1.00 AC: 2 AN: 2

European-Finnish (FIN) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.536 AC: 15 AN: 28

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.625 AC: 94952 AN: 151998 Hom.: 31494 Cov.: 31 AF XY: 0.630 AC XY: 46835 AN XY: 74286

African (AFR) AF: 0.818 AC: 33934 AN: 41484

American (AMR) AF: 0.588 AC: 8995 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 1718 AN: 3470

East Asian (EAS) AF: 0.958 AC: 4912 AN: 5128

South Asian (SAS) AF: 0.756 AC: 3646 AN: 4822

European-Finnish (FIN) AF: 0.593 AC: 6272 AN: 10568

Middle Eastern (MID) AF: 0.534 AC: 156 AN: 292

European-Non Finnish (NFE) AF: 0.494 AC: 33554 AN: 67926

Other (OTH) AF: 0.591 AC: 1246 AN: 2108

Alfa AF: 0.553 Hom.: 3059

Bravo AF: 0.630

Asia WGS AF: 0.847 AC: 2942 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.5
DANN	Benign	0.59
PhyloP100		0.41

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1919364; hg19: chr15-33009574;