NM_013372.7:c.-1-3347C>T

Variant names:

• chr15-32727343-C-T
• rs11071928
• NM_013372.7:c.-1-3347C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_013372.7(GREM1):​c.-1-3347C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 152,020 control chromosomes in the GnomAD database, including 19,755 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.50 (19755 hom., cov: 32)
• Consequence: GREM1 NM_013372.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.04
• Publications: 3 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 15-32727343-C-T is Benign according to our data. Variant chr15-32727343-C-T is described in ClinVar as Benign. ClinVar VariationId is 1277057.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GREM1	NM_013372.7	c.-1-3347C>T		intron_variant	Intron 1 of 1	ENST00000651154.1	NP_037504.1
GREM1	NM_001368719.1	c.-1-3347C>T		intron_variant	Intron 1 of 1		NP_001355648.1
GREM1	NM_001191323.2	c.-1-3347C>T		intron_variant	Intron 1 of 2		NP_001178252.1
GREM1	NM_001191322.2	c.-1-3347C>T		intron_variant	Intron 1 of 2		NP_001178251.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GREM1	ENST00000651154.1	c.-1-3347C>T		intron_variant	Intron 1 of 1		NM_013372.7	ENSP00000498748.1
GREM1	ENST00000560677.5	c.-1-3347C>T		intron_variant	Intron 1 of 2	4		ENSP00000453387.1
GREM1	ENST00000652365.1	c.-1-3347C>T		intron_variant	Intron 1 of 1			ENSP00000498763.1
GREM1	ENST00000560830.1	c.-1-3347C>T		intron_variant	Intron 1 of 2	2		ENSP00000453141.1

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75316 AN: 151900 Hom.: 19752 Cov.: 32

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.519

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.496 AC: 75347 AN: 152020 Hom.: 19755 Cov.: 32 AF XY: 0.499 AC XY: 37041 AN XY: 74298

African (AFR) AF: 0.306 AC: 12691 AN: 41448

American (AMR) AF: 0.531 AC: 8113 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.585 AC: 2026 AN: 3466

East Asian (EAS) AF: 0.553 AC: 2860 AN: 5174

South Asian (SAS) AF: 0.543 AC: 2613 AN: 4814

European-Finnish (FIN) AF: 0.573 AC: 6053 AN: 10564

Middle Eastern (MID) AF: 0.582 AC: 170 AN: 292

European-Non Finnish (NFE) AF: 0.578 AC: 39299 AN: 67966

Other (OTH) AF: 0.522 AC: 1105 AN: 2116

Alfa AF: 0.532 Hom.: 2739

Bravo AF: 0.483

Asia WGS AF: 0.518 AC: 1807 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 05, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.064
DANN	Benign	0.79
PhyloP100		-1.0
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: rs11071928; hg19: chr15-33019544;