chr1-240553161-C-A

Variant names:

• chr1-240553161-C-A
• rs7411138
• NM_022469.4:c.-2+58723G>T

Variant summary

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

The NM_022469.4(GREM2):​c.-2+58723G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,100 control chromosomes in the GnomAD database, including 2,660 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 0.16 (2660 hom., cov: 33)
• Consequence: GREM2 NM_022469.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.236
• Publications: 1 publications found

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]

ENSG00000300002 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GREM2	NM_022469.4	c.-2+58723G>T		intron_variant	Intron 1 of 1	ENST00000318160.5	NP_071914.3
GREM2	XM_047427832.1	c.-276-21198G>T		intron_variant	Intron 1 of 2		XP_047283788.1
GREM2	XM_047427839.1	c.-277+17732G>T		intron_variant	Intron 2 of 3		XP_047283795.1
GREM2	XM_011544249.3	c.-121-55564G>T		intron_variant	Intron 1 of 2		XP_011542551.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GREM2	ENST00000318160.5	c.-2+58723G>T		intron_variant	Intron 1 of 1	1	NM_022469.4	ENSP00000318650.4
ENSG00000300002	ENST00000767897.1	n.376+17732G>T		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23759 AN: 151982 Hom.: 2648 Cov.: 33

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.0982

Gnomad EAS AF: 0.0844

Gnomad SAS AF: 0.0601

Gnomad FIN AF: 0.0682

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0942

Gnomad OTH AF: 0.143

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.157 AC: 23809 AN: 152100 Hom.: 2660 Cov.: 33 AF XY: 0.153 AC XY: 11414 AN XY: 74370

African (AFR) AF: 0.313 AC: 12966 AN: 41466

American (AMR) AF: 0.151 AC: 2312 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0982 AC: 341 AN: 3472

East Asian (EAS) AF: 0.0848 AC: 437 AN: 5156

South Asian (SAS) AF: 0.0604 AC: 291 AN: 4820

European-Finnish (FIN) AF: 0.0682 AC: 723 AN: 10596

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0942 AC: 6408 AN: 67992

Other (OTH) AF: 0.143 AC: 303 AN: 2116

Alfa AF: 0.125 Hom.: 398

Bravo AF: 0.174

Asia WGS AF: 0.0790 AC: 275 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	14
DANN	Benign	0.86
PhyloP100		0.24
Mutation Taster		=100/0	polymorphism (auto)

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: rs7411138; hg19: chr1-240716461;