1-240509503-T-G

Position:

• chr1-240509503-T-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The ENST00000318160.5(GREM2):​c.-1-16027A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 151,698 control chromosomes in the GnomAD database, including 1,905 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency: Genomes: 𝑓 0.14 (1905 hom., cov: 29)
• Consequence: GREM2 ENST00000318160.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.841

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 1-240509503-T-G is Benign according to our data. Variant chr1-240509503-T-G is described in ClinVar as [Benign]. Clinvar id is 873242.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GREM2	NM_022469.4	c.-1-16027A>C		intron_variant		ENST00000318160.5	NP_071914.3
GREM2	XM_011544249.3	c.-121-11906A>C		intron_variant			XP_011542551.1
GREM2	XM_047427832.1	c.54-16027A>C		intron_variant			XP_047283788.1
GREM2	XM_047427839.1	c.54-16027A>C		intron_variant			XP_047283795.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GREM2	ENST00000318160.5	c.-1-16027A>C		intron_variant		1	NM_022469.4	ENSP00000318650	P1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21853 AN: 151582 Hom.: 1897 Cov.: 29

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.000585

Gnomad SAS AF: 0.0162

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.128

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.144 AC: 21904 AN: 151698 Hom.: 1905 Cov.: 29 AF XY: 0.143 AC XY: 10613 AN XY: 74162

Gnomad4 AFR AF: 0.237

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.000586

Gnomad4 SAS AF: 0.0165

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.116

Gnomad4 OTH AF: 0.151

Alfa AF: 0.0409 Hom.: 33

Bravo AF: 0.148

Asia WGS AF: 0.0300 AC: 103 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

case-control

Suna and Inan Kirac Foundation Neurodegeneration Research Laboratory, Koc University

Apr 02, 2020

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.59

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

Other links and lift over

dbSNP: rs61832588; hg19: chr1-240672803;