NM_013372.7:c.-23C>G

Variant names:

• chr15-32718140-C-G
• rs572282473
• NM_013372.7:c.-23C>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_013372.7(GREM1):​c.-23C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000159 in 1,311,936 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00068 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000091 (2 hom.)
• Consequence: GREM1 NM_013372.7 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.12
• 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 15-32718140-C-G is Benign according to our data. Variant chr15-32718140-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1697738.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 103 AD gene.

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.-23C>G		5_prime_UTR	Exon 1 of 2	NP_037504.1	A6XAA7
	GREM1	NM_001191323.2		c.-23C>G		5_prime_UTR	Exon 1 of 3	NP_001178252.1	O60565-2
	GREM1	NM_001191322.2		c.-23C>G		5_prime_UTR	Exon 1 of 3	NP_001178251.1	B3KTR9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GREM1	ENST00000651154.1	MANE Select	c.-23C>G		5_prime_UTR	Exon 1 of 2	ENSP00000498748.1	O60565-1
	GREM1	ENST00000560677.5	TSL:4	c.-23C>G		5_prime_UTR	Exon 1 of 3	ENSP00000453387.1	H0YLY2
	GREM1	ENST00000560830.1	TSL:2	c.-23C>G		5_prime_UTR	Exon 1 of 3	ENSP00000453141.1	O60565-2

Frequencies

GnomAD3 genomes AF: 0.000678 AC: 103 AN: 152002 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00215

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000141 AC: 14 AN: 99184 AF XY: 0.0000569

Gnomad AFR exome AF: 0.00120

Gnomad AMR exome AF: 0.0000937

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000836

Gnomad OTH exome AF: 0.000313

GnomAD4 exome AF: 0.0000914 AC: 106 AN: 1159816 Hom.: 2 Cov.: 30 AF XY: 0.0000698 AC XY: 39 AN XY: 558996

African (AFR) AF: 0.00209 AC: 56 AN: 26806

American (AMR) AF: 0.0000743 AC: 2 AN: 26936

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17344

East Asian (EAS) AF: 0.00 AC: 0 AN: 23008

South Asian (SAS) AF: 0.0000866 AC: 6 AN: 69322

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10840

Middle Eastern (MID) AF: 0.000444 AC: 2 AN: 4504

European-Non Finnish (NFE) AF: 0.0000150 AC: 14 AN: 935822

Other (OTH) AF: 0.000575 AC: 26 AN: 45234

GnomAD4 genome AF: 0.000677 AC: 103 AN: 152120 Hom.: 0 Cov.: 31 AF XY: 0.000699 AC XY: 52 AN XY: 74376

African (AFR) AF: 0.00212 AC: 88 AN: 41528

American (AMR) AF: 0.000719 AC: 11 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5138

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67942

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.0000435 Hom.: 0

Bravo AF: 0.000740

ClinVar

ClinVar submissions as Germline

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	-0.81
CADD	Benign	3.6
DANN	Benign	0.62
PhyloP100		-3.1
PromoterAI		0.049	Neutral
Mutation Taster		=300/0	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: rs572282473; hg19: chr15-33010341;