15-32718170-G-C

Variant names:

• chr15-32718170-G-C
• rs1318786176
• NM_013372.7:c.-2+9G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_013372.7(GREM1):​c.-2+9G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000253 in 1,183,582 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000025 (0 hom.)
• Consequence: GREM1 NM_013372.7 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.703
• 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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 15-32718170-G-C is Benign according to our data. Variant chr15-32718170-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1697739.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013372.7. 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.-2+9G>C		intron	N/A	NP_037504.1	A6XAA7
	GREM1	NM_001191323.2		c.-2+9G>C		intron	N/A	NP_001178252.1	O60565-2
	GREM1	NM_001191322.2		c.-2+9G>C		intron	N/A	NP_001178251.1	B3KTR9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GREM1	ENST00000651154.1	MANE Select	c.-2+9G>C		intron	N/A	ENSP00000498748.1	O60565-1
	GREM1	ENST00000560677.5	TSL:4	c.-2+9G>C		intron	N/A	ENSP00000453387.1	H0YLY2
	GREM1	ENST00000908783.1		c.-2+1060G>C		intron	N/A	ENSP00000578842.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00 AC: 0 AN: 122218 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000253 AC: 3 AN: 1183582 Hom.: 0 Cov.: 30 AF XY: 0.00000174 AC XY: 1 AN XY: 573972

African (AFR) AF: 0.0000367 AC: 1 AN: 27240

American (AMR) AF: 0.00 AC: 0 AN: 29532

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19246

East Asian (EAS) AF: 0.00 AC: 0 AN: 22984

South Asian (SAS) AF: 0.00 AC: 0 AN: 74358

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12258

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4716

European-Non Finnish (NFE) AF: 0.00000211 AC: 2 AN: 947122

Other (OTH) AF: 0.00 AC: 0 AN: 46126

GnomAD4 genome Cov.: 31

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	-0.69
CADD	Benign	9.6
DANN	Benign	0.86
PhyloP100		-0.70
PromoterAI		0.022	Neutral
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs1318786176; hg19: chr15-33010371;