rs3743105

chr15-32731750-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013372.7(GREM1):c.*505T>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 0.528 in 242,012 control chromosomes in the GnomAD database, including 36,432 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.49 (20503 hom., cov: 31)
  • Exomes 𝑓: 0.59 (15929 hom.)
• Consequence: GREM1 NM_013372.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• 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/exons	MANE	UniProt
GREM1	NM_013372.7	c.*505T>C		3_prime_UTR_variant	2/2	ENST00000651154.1
GREM1	NM_001191322.2	c.*505T>C		3_prime_UTR_variant	3/3
GREM1	NM_001191323.2	c.*505T>C		3_prime_UTR_variant	3/3
GREM1	NM_001368719.1	c.*505T>C		3_prime_UTR_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GREM1	ENST00000651154.1	c.*505T>C		3_prime_UTR_variant	2/2		NM_013372.7	P1
GREM1	ENST00000560830.1	c.*505T>C		3_prime_UTR_variant	3/3	2
GREM1	ENST00000652365.1	c.*505T>C		3_prime_UTR_variant	2/2			P1

Frequencies

GnomAD3 genomes AF: 0.494 AC: 74993 AN: 151868 Hom.: 20499 Cov.: 31

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.769

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.515

GnomAD4 exome AF: 0.587 AC: 52833 AN: 90026 Hom.: 15929 Cov.: 0 AF XY: 0.592 AC XY: 24903 AN XY: 42060

Gnomad4 AFR exome AF: 0.234

Gnomad4 AMR exome AF: 0.516

Gnomad4 ASJ exome AF: 0.585

Gnomad4 EAS exome AF: 0.675

Gnomad4 SAS exome AF: 0.587

Gnomad4 FIN exome AF: 0.613

Gnomad4 NFE exome AF: 0.593

Gnomad4 OTH exome AF: 0.564

GnomAD4 genome AF: 0.494 AC: 75014 AN: 151986 Hom.: 20503 Cov.: 31 AF XY: 0.500 AC XY: 37168 AN XY: 74266

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.528

Gnomad4 ASJ AF: 0.606

Gnomad4 EAS AF: 0.768

Gnomad4 SAS AF: 0.621

Gnomad4 FIN AF: 0.612

Gnomad4 NFE AF: 0.583

Gnomad4 OTH AF: 0.521

Alfa AF: 0.560 Hom.: 34162

Bravo AF: 0.476

Asia WGS AF: 0.638 AC: 2220 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	7.0
Dann	Benign	0.59

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: rs3743105; hg19: chr15-33023951;