rs7176378

Positions:

• chr15-32734978-T-A
• chr15-32734978-T-C
• chr15-32734978-T-G

Variant summary

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

The NM_013372.7(GREM1):​c.*3733T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.805 in 154,388 control chromosomes in the GnomAD database, including 50,553 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 0.81 (49842 hom., cov: 31)
  • Exomes 𝑓: 0.80 (711 hom.)
• Consequence: GREM1 NM_013372.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.157

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GREM1	NM_013372.7	c.*3733T>A		3_prime_UTR_variant	2/2	ENST00000651154.1
GREM1	NM_001368719.1	c.*3733T>A		3_prime_UTR_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GREM1	ENST00000651154.1	c.*3733T>A		3_prime_UTR_variant	2/2		NM_013372.7	P1

Frequencies

GnomAD3 genomes AF: 0.805 AC: 122386 AN: 152034 Hom.: 49786 Cov.: 31

Gnomad AFR AF: 0.898

Gnomad AMI AF: 0.834

Gnomad AMR AF: 0.819

Gnomad ASJ AF: 0.751

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.852

Gnomad FIN AF: 0.814

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.729

Gnomad OTH AF: 0.782

GnomAD4 exome AF: 0.797 AC: 1781 AN: 2236 Hom.: 711 Cov.: 0 AF XY: 0.795 AC XY: 808 AN XY: 1016

Gnomad4 AFR exome AF: 0.853

Gnomad4 AMR exome AF: 0.795

Gnomad4 ASJ exome AF: 0.722

Gnomad4 EAS exome AF: 0.998

Gnomad4 SAS exome AF: 0.818

Gnomad4 NFE exome AF: 0.744

Gnomad4 OTH exome AF: 0.732

GnomAD4 genome AF: 0.805 AC: 122502 AN: 152152 Hom.: 49842 Cov.: 31 AF XY: 0.811 AC XY: 60287 AN XY: 74382

Gnomad4 AFR AF: 0.898

Gnomad4 AMR AF: 0.819

Gnomad4 ASJ AF: 0.751

Gnomad4 EAS AF: 0.997

Gnomad4 SAS AF: 0.852

Gnomad4 FIN AF: 0.814

Gnomad4 NFE AF: 0.729

Gnomad4 OTH AF: 0.784

Alfa AF: 0.770 Hom.: 5627

Bravo AF: 0.810

Asia WGS AF: 0.910 AC: 3165 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.2
DANN	Benign	0.70

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: rs7176378; hg19: chr15-33027179;