ENST00000558441.1:n.1054G>A

Variant names:

• chr15-32717954-C-T
• rs1027151448
• ENST00000908783.1:c.-2+844C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The ENST00000558441.1(GREM1-AS1):​n.1054G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,022,238 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000024 (0 hom.)
• Consequence: GREM1-AS1 ENST00000558441.1 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.210
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BP6: Variant 15-32717954-C-T is Benign according to our data. Variant chr15-32717954-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2576282.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000558441.1. 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
	GREM1	NM_013372.7	MANE Select	c.-209C>T		upstream_gene	N/A	NP_037504.1	A6XAA7
	GREM1	NM_001191323.2		c.-209C>T		upstream_gene	N/A	NP_001178252.1	O60565-2
	GREM1	NM_001191322.2		c.-209C>T		upstream_gene	N/A	NP_001178251.1	B3KTR9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GREM1	ENST00000908783.1		c.-2+844C>T		intron	N/A	ENSP00000578842.1
	GREM1-AS1	ENST00000558441.1	TSL:6	n.1054G>A		non_coding_transcript_exon	Exon 1 of 1
	GREM1	ENST00000651154.1	MANE Select	c.-209C>T		upstream_gene	N/A	ENSP00000498748.1	O60565-1

Frequencies

GnomAD3 genomes AF: 0.0000330 AC: 5 AN: 151664 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000737

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000241 AC: 21 AN: 870574 Hom.: 0 Cov.: 16 AF XY: 0.0000174 AC XY: 7 AN XY: 402814

African (AFR) AF: 0.00 AC: 0 AN: 17940

American (AMR) AF: 0.00 AC: 0 AN: 2688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8752

East Asian (EAS) AF: 0.00 AC: 0 AN: 12668

South Asian (SAS) AF: 0.00 AC: 0 AN: 17042

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 552

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1946

European-Non Finnish (NFE) AF: 0.0000244 AC: 19 AN: 777382

Other (OTH) AF: 0.0000633 AC: 2 AN: 31604

GnomAD4 genome AF: 0.0000330 AC: 5 AN: 151664 Hom.: 0 Cov.: 31 AF XY: 0.0000270 AC XY: 2 AN XY: 74094

African (AFR) AF: 0.00 AC: 0 AN: 41318

American (AMR) AF: 0.00 AC: 0 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5054

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10568

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000737 AC: 5 AN: 67878

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000378

ClinVar

ClinVar submissions

Significance: Likely 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	-0.26
CADD	Benign	18
DANN	Uncertain	0.98
PhyloP100		0.21
PromoterAI		-0.11	Neutral

Splicing

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

Other links and lift over

dbSNP: rs1027151448; hg19: chr15-33010155;