15-32718041-A-T

Variant names:

• chr15-32718041-A-T
• rs537464935
• NM_013372.7:c.-122A>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_013372.7(GREM1):​c.-122A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000846 in 1,158,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00028 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000056 (0 hom.)
• Consequence: GREM1 NM_013372.7 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0550
• 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 15-32718041-A-T is Benign according to our data. Variant chr15-32718041-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 2575157.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 42 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GREM1	NM_013372.7	c.-122A>T		5_prime_UTR_variant	Exon 1 of 2	ENST00000651154.1	NP_037504.1
GREM1	NM_001191323.2	c.-122A>T		5_prime_UTR_variant	Exon 1 of 3		NP_001178252.1
GREM1	NM_001191322.2	c.-122A>T		5_prime_UTR_variant	Exon 1 of 3		NP_001178251.1
GREM1-AS1	NR_109767.1	n.*60T>A		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GREM1	ENST00000651154.1	c.-122A>T		5_prime_UTR_variant	Exon 1 of 2		NM_013372.7	ENSP00000498748.1
GREM1	ENST00000560677.5	c.-122A>T		5_prime_UTR_variant	Exon 1 of 3	4		ENSP00000453387.1

Frequencies

GnomAD3 genomes AF: 0.000283 AC: 43 AN: 151820 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00684

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000480

GnomAD2 exomes AF: 0.000471 AC: 3 AN: 6376 AF XY: 0.000294

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00272

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000556 AC: 56 AN: 1006942 Hom.: 0 Cov.: 30 AF XY: 0.0000548 AC XY: 26 AN XY: 474830

African (AFR) AF: 0.00 AC: 0 AN: 19574

American (AMR) AF: 0.00 AC: 0 AN: 4974

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11550

East Asian (EAS) AF: 0.00190 AC: 30 AN: 15806

South Asian (SAS) AF: 0.000320 AC: 13 AN: 40582

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6974

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2430

European-Non Finnish (NFE) AF: 0.00000115 AC: 1 AN: 866634

Other (OTH) AF: 0.000312 AC: 12 AN: 38418

GnomAD4 genome AF: 0.000276 AC: 42 AN: 151928 Hom.: 0 Cov.: 31 AF XY: 0.000364 AC XY: 27 AN XY: 74274

African (AFR) AF: 0.00 AC: 0 AN: 41462

American (AMR) AF: 0.0000654 AC: 1 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00667 AC: 34 AN: 5098

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10560

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67924

Other (OTH) AF: 0.000475 AC: 1 AN: 2106

Alfa AF: 0.000356 Hom.: 0

Bravo AF: 0.000215

Asia WGS AF: 0.00522 AC: 18 AN: 3460

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	13
DANN	Benign	0.93
PhyloP100		-0.055
PromoterAI		0.089	Neutral
Mutation Taster		=271/29	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: rs537464935; hg19: chr15-33010242;