chr15-32718091-G-T

Variant names:

• chr15-32718091-G-T
• rs568143803
• NM_013372.7:c.-72G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_013372.7(GREM1):​c.-72G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000935 in 1,069,048 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 9.4e-7 (0 hom.)
• Consequence: GREM1 NM_013372.7 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.851
• Publications: 0 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-AS1 (HGNC:55411): (GREM1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GREM1	NM_013372.7	c.-72G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 2	ENST00000651154.1	NP_037504.1
GREM1	NM_013372.7	c.-72G>T		5_prime_UTR_variant	Exon 1 of 2	ENST00000651154.1	NP_037504.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GREM1	ENST00000651154.1	c.-72G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 2		NM_013372.7	ENSP00000498748.1
GREM1	ENST00000560677.5	c.-72G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 3	4		ENSP00000453387.1
GREM1	ENST00000651154.1	c.-72G>T		5_prime_UTR_variant	Exon 1 of 2		NM_013372.7	ENSP00000498748.1
GREM1	ENST00000560677.5	c.-72G>T		5_prime_UTR_variant	Exon 1 of 3	4		ENSP00000453387.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 9.35e-7 AC: 1 AN: 1069048 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 509054

African (AFR) AF: 0.00 AC: 0 AN: 20576

American (AMR) AF: 0.00 AC: 0 AN: 10246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12834

East Asian (EAS) AF: 0.00 AC: 0 AN: 18762

South Asian (SAS) AF: 0.00 AC: 0 AN: 53792

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8764

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3212

European-Non Finnish (NFE) AF: 0.00000111 AC: 1 AN: 899556

Other (OTH) AF: 0.00 AC: 0 AN: 41306

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	21
DANN	Benign	0.97
PhyloP100		0.85
PromoterAI		0.023	Neutral
Mutation Taster		=289/11	polymorphism

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: rs568143803; hg19: chr15-33010292;