chr15-32720031-T-C

Position:

• chr15-32720031-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_013372.7(GREM1):​c.-2+1870T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 152,142 control chromosomes in the GnomAD database, including 7,538 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.29 (7538 hom., cov: 32)
• Consequence: GREM1 NM_013372.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.434

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 15-32720031-T-C is Benign according to our data. Variant chr15-32720031-T-C is described in ClinVar as [Benign]. Clinvar id is 1294086.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GREM1	NM_013372.7	c.-2+1870T>C		intron_variant		ENST00000651154.1
GREM1	NM_001191322.2	c.-2+1870T>C		intron_variant
GREM1	NM_001191323.2	c.-2+1870T>C		intron_variant
GREM1	NM_001368719.1	c.-2+1329T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GREM1	ENST00000651154.1	c.-2+1870T>C		intron_variant			NM_013372.7	P1
GREM1	ENST00000560677.5	c.-2+1870T>C		intron_variant		4
GREM1	ENST00000560830.1	c.-2+1870T>C		intron_variant		2
GREM1	ENST00000652365.1	c.-2+1329T>C		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43872 AN: 152024 Hom.: 7535 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.0412

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.315

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

GnomAD4 genome AF: 0.288 AC: 43882 AN: 152142 Hom.: 7538 Cov.: 32 AF XY: 0.285 AC XY: 21229 AN XY: 74368

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.330

Gnomad4 ASJ AF: 0.456

Gnomad4 EAS AF: 0.0413

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.319

Gnomad4 NFE AF: 0.389

Gnomad4 OTH AF: 0.314

Alfa AF: 0.363 Hom.: 2463

Bravo AF: 0.283

Asia WGS AF: 0.131 AC: 460 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	12
DANN	Benign	0.81

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

Publications

LitVar

Other links and lift over

dbSNP: rs11635984; hg19: chr15-33012232;