dbSNP rs3748538: GREM2:c.-1-37226C>T (chr1-240530702-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.367

Publications

1 publications found

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]

GREM2 links:

ENSG00000224359 (HGNC:):

ENSG00000224359 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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	Effect	Exon rank	MANE	Protein	UniProt
GREM2	NM_022469.4 link	c.-1-37226C>T	intron_variant	Intron 1 of 1	ENST00000318160.5	NP_071914.3
GREM2	XM_047427832.1 link	c.53+933C>T	intron_variant	Intron 2 of 2		XP_047283788.1
GREM2	XM_047427839.1 link	c.53+933C>T	intron_variant	Intron 3 of 3		XP_047283795.1
GREM2	XM_011544249.3 link	c.-121-33105C>T	intron_variant	Intron 1 of 2		XP_011542551.1	Q9H772

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GREM2	ENST00000318160.5 link	c.-1-37226C>T		intron_variant	Intron 1 of 1	1	NM_022469.4	ENSP00000318650.4		Q9H772
ENSG00000224359	ENST00000457477.2 link	n.197G>A		non_coding_transcript_exon_variant	Exon 2 of 2	5

Frequencies

GnomAD3 genomes

AF:

0.278

AC:

42171

AN:

151966

Hom.:

6766

Cov.:

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:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.278

AC:

42208

AN:

152084

Hom.:

6770

Cov.:

AF XY:

0.275

AC XY:

20414

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.145

AC:

6027

AN:

41500

American (AMR)

AF:

0.360

AC:

5494

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.187

AC:

650

AN:

3470

East Asian (EAS)

AF:

0.0838

AC:

434

AN:

5180

South Asian (SAS)

AF:

0.237

AC:

1142

AN:

4824

European-Finnish (FIN)

AF:

0.323

AC:

3415

AN:

10558

Middle Eastern (MID)

AF:

0.187

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.358

AC:

24321

AN:

67970

Other (OTH)

AF:

0.268

AC:

565

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1500

3000

4501

6001

7501

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

422

844

1266

1688

2110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.49

PhyloP100

0.37

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over