rs11071928

Positions:

• chr15-32727343-C-T

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.-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

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=-0.96).
• BP6: Variant 15-32727343-C-T is Benign according to our data. Variant chr15-32727343-C-T is described in ClinVar as [Benign]. Clinvar id 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/exons	MANE	Protein	UniProt
GREM1	NM_013372.7	c.-1-3347C>T		intron_variant		ENST00000651154.1	NP_037504.1
GREM1	NM_001191322.2	c.-1-3347C>T		intron_variant			NP_001178251.1
GREM1	NM_001191323.2	c.-1-3347C>T		intron_variant			NP_001178252.1
GREM1	NM_001368719.1	c.-1-3347C>T		intron_variant			NP_001355648.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GREM1	ENST00000651154.1	c.-1-3347C>T		intron_variant			NM_013372.7	ENSP00000498748	P1
GREM1	ENST00000560677.5	c.-1-3347C>T		intron_variant		4		ENSP00000453387
GREM1	ENST00000560830.1	c.-1-3347C>T		intron_variant		2		ENSP00000453141
GREM1	ENST00000652365.1	c.-1-3347C>T		intron_variant				ENSP00000498763	P1

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

Gnomad4 AFR AF: 0.306

Gnomad4 AMR AF: 0.531

Gnomad4 ASJ AF: 0.585

Gnomad4 EAS AF: 0.553

Gnomad4 SAS AF: 0.543

Gnomad4 FIN AF: 0.573

Gnomad4 NFE AF: 0.578

Gnomad4 OTH AF: 0.522

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.064
DANN	Benign	0.79

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: rs11071928; hg19: chr15-33019544;