ENST00000558441.1:n.1731T>A

Variant names:

• chr15-32717277-A-T
• rs1406389
• ENST00000908783.1:c.-2+167A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000558441.1(GREM1-AS1):​n.1731T>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,104 control chromosomes in the GnomAD database, including 5,191 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 0.24 (5191 hom., cov: 33)
  • Exomes 𝑓: 0.27 (0 hom.)
• Consequence: GREM1-AS1 ENST00000558441.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.355
• Publications: 18 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000558441.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GREM1	ENST00000908783.1		c.-2+167A>T		intron	N/A	ENSP00000578842.1
	GREM1-AS1	ENST00000558441.1	TSL:6	n.1731T>A		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36964 AN: 151964 Hom.: 5185 Cov.: 33

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.685

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.233

GnomAD4 exome AF: 0.273 AC: 6 AN: 22 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 5 AN XY: 20

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.273 AC: 6 AN: 22

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.243 AC: 36989 AN: 152082 Hom.: 5191 Cov.: 33 AF XY: 0.249 AC XY: 18509 AN XY: 74364

African (AFR) AF: 0.258 AC: 10688 AN: 41496

American (AMR) AF: 0.195 AC: 2977 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 566 AN: 3466

East Asian (EAS) AF: 0.684 AC: 3538 AN: 5176

South Asian (SAS) AF: 0.339 AC: 1633 AN: 4818

European-Finnish (FIN) AF: 0.300 AC: 3177 AN: 10576

Middle Eastern (MID) AF: 0.192 AC: 56 AN: 292

European-Non Finnish (NFE) AF: 0.203 AC: 13766 AN: 67952

Other (OTH) AF: 0.239 AC: 505 AN: 2112

Alfa AF: 0.217 Hom.: 501

Bravo AF: 0.237

Asia WGS AF: 0.480 AC: 1669 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.9
DANN	Benign	0.66
PhyloP100		0.35

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1406389; hg19: chr15-33009478;