rs17816260

Variant names:

• chr15-32731484-A-C
• rs17816260
• NM_013372.7:c.*239A>C

Your query was ambiguous. Multiple possible variants found:

• chr15-32731484-A-C
• chr15-32731484-A-G
• chr15-32731484-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_013372.7(GREM1):​c.*239A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 564,408 control chromosomes in the GnomAD database, including 92,051 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.49 (20292 hom., cov: 31)
  • Exomes 𝑓: 0.59 (71759 hom.)
• Consequence: GREM1 NM_013372.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.939
• Publications: 11 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 Gene-Disease associations (from GenCC):

• hereditary mixed polyposis syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet, G2P
• polyposis syndrome, hereditary mixed, 1

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 15-32731484-A-C is Benign according to our data. Variant chr15-32731484-A-C is described in ClinVar as Benign. ClinVar VariationId is 1278747.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GREM1	NM_013372.7	c.*239A>C		3_prime_UTR_variant	Exon 2 of 2	ENST00000651154.1	NP_037504.1
GREM1	NM_001368719.1	c.*239A>C		3_prime_UTR_variant	Exon 2 of 2		NP_001355648.1
GREM1	NM_001191323.2	c.*239A>C		3_prime_UTR_variant	Exon 3 of 3		NP_001178252.1
GREM1	NM_001191322.2	c.*239A>C		3_prime_UTR_variant	Exon 3 of 3		NP_001178251.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GREM1	ENST00000651154.1	c.*239A>C		3_prime_UTR_variant	Exon 2 of 2		NM_013372.7	ENSP00000498748.1
GREM1	ENST00000652365.1	c.*239A>C		3_prime_UTR_variant	Exon 2 of 2			ENSP00000498763.1
GREM1	ENST00000560830.1	c.*239A>C		3_prime_UTR_variant	Exon 3 of 3	2		ENSP00000453141.1
GREM1	ENST00000560677.5	c.*544A>C		downstream_gene_variant		4		ENSP00000453387.1

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74641 AN: 151780 Hom.: 20289 Cov.: 31

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.769

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.581

Gnomad OTH AF: 0.516

GnomAD4 exome AF: 0.586 AC: 241589 AN: 412510 Hom.: 71759 Cov.: 2 AF XY: 0.589 AC XY: 126261 AN XY: 214492

African (AFR) AF: 0.240 AC: 2720 AN: 11328

American (AMR) AF: 0.523 AC: 7531 AN: 14402

Ashkenazi Jewish (ASJ) AF: 0.593 AC: 7580 AN: 12780

East Asian (EAS) AF: 0.707 AC: 20004 AN: 28302

South Asian (SAS) AF: 0.612 AC: 21943 AN: 35856

European-Finnish (FIN) AF: 0.612 AC: 25116 AN: 41024

Middle Eastern (MID) AF: 0.585 AC: 1066 AN: 1822

European-Non Finnish (NFE) AF: 0.584 AC: 141970 AN: 243210

Other (OTH) AF: 0.574 AC: 13659 AN: 23786

GnomAD4 genome AF: 0.492 AC: 74662 AN: 151898 Hom.: 20292 Cov.: 31 AF XY: 0.499 AC XY: 37019 AN XY: 74240

African (AFR) AF: 0.244 AC: 10085 AN: 41416

American (AMR) AF: 0.522 AC: 7975 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.606 AC: 2102 AN: 3470

East Asian (EAS) AF: 0.768 AC: 3934 AN: 5120

South Asian (SAS) AF: 0.623 AC: 2991 AN: 4802

European-Finnish (FIN) AF: 0.611 AC: 6450 AN: 10564

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.581 AC: 39442 AN: 67938

Other (OTH) AF: 0.521 AC: 1098 AN: 2108

Alfa AF: 0.516 Hom.: 7995

Bravo AF: 0.473

Asia WGS AF: 0.639 AC: 2225 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jul 06, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.35
DANN	Benign	0.40
PhyloP100		-0.94
Mutation Taster		=100/0	polymorphism (auto)

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: rs17816260; hg19: chr15-33023685;