rs3748538

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_022469.4(GREM2):​c.-1-37226C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 152,084 control chromosomes in the GnomAD database, including 6,770 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 0.28 ( 6770 hom., cov: 33)
Failed GnomAD Quality Control

Consequence

GREM2
NM_022469.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.367
Variant links:
Genes affected
GREM2 (HGNC:17655): (gremlin 2, 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. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.95).
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GREM2NM_022469.4 linkuse as main transcriptc.-1-37226C>T intron_variant ENST00000318160.5 NP_071914.3
GREM2XM_011544249.3 linkuse as main transcriptc.-121-33105C>T intron_variant XP_011542551.1
GREM2XM_047427832.1 linkuse as main transcriptc.53+933C>T intron_variant XP_047283788.1
GREM2XM_047427839.1 linkuse as main transcriptc.53+933C>T intron_variant XP_047283795.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GREM2ENST00000318160.5 linkuse as main transcriptc.-1-37226C>T intron_variant 1 NM_022469.4 ENSP00000318650 P1
ENST00000457477.2 linkuse as main transcriptn.197G>A non_coding_transcript_exon_variant 2/25

Frequencies

GnomAD3 genomes
AF:
0.278
AC:
42171
AN:
151966
Hom.:
6766
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.145
Gnomad AMI
AF:
0.115
Gnomad AMR
AF:
0.360
Gnomad ASJ
AF:
0.187
Gnomad EAS
AF:
0.0840
Gnomad SAS
AF:
0.236
Gnomad FIN
AF:
0.323
Gnomad MID
AF:
0.174
Gnomad NFE
AF:
0.358
Gnomad OTH
AF:
0.265
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AC:
0
AN:
0
Hom.:
0
Cov.:
0
AC XY:
0
AN XY:
0
GnomAD4 genome
AF:
0.278
AC:
42208
AN:
152084
Hom.:
6770
Cov.:
33
AF XY:
0.275
AC XY:
20414
AN XY:
74348
show subpopulations
Gnomad4 AFR
AF:
0.145
Gnomad4 AMR
AF:
0.360
Gnomad4 ASJ
AF:
0.187
Gnomad4 EAS
AF:
0.0838
Gnomad4 SAS
AF:
0.237
Gnomad4 FIN
AF:
0.323
Gnomad4 NFE
AF:
0.358
Gnomad4 OTH
AF:
0.268
Alfa
AF:
0.323
Hom.:
1410
Bravo
AF:
0.271
Asia WGS
AF:
0.183
AC:
635
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.95
CADD
Benign
3.4
DANN
Benign
0.49

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs3748538; hg19: chr1-240694002; API