Variant 12-55743400-CGCGGCGGCGGCGGCGGCG-CGCGGCGGCGGCGGCG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP3BP6BS1BS2

The NM_005811.5(GDF11):c.114_116delGGC(p.Ala39del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00696 in 965,392 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0080 ( 0 hom. )

Consequence

GDF11
NM_005811.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.25

Variant links:

Genes affected

GDF11 (HGNC:4216): (growth differentiation factor 11) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. This protein plays a role in the development of the nervous and other organ systems, and may regulate aging. [provided by RefSeq, Aug 2016]

GDF11 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_005811.5

BP6

Variant 12-55743400-CGCG-C is Benign according to our data. Variant chr12-55743400-CGCG-C is described in ClinVar as [Likely_benign]. Clinvar id is 3054165.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr12-55743400-CGCG-C is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00799 (6552/819642) while in subpopulation AMR AF= 0.0214 (29/1358). AF 95% confidence interval is 0.0153. There are 0 homozygotes in gnomad4_exome. There are 3122 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

BS2

High AC in GnomAd4 at 163 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GDF11	NM_005811.5 link	c.114_116delGGC	p.Ala39del	disruptive_inframe_deletion	Exon 1 of 3	ENST00000257868.10	NP_005802.1	O95390A0A024RB20
GDF11	XM_006719194.4 link	c.114_116delGGC	p.Ala39del	disruptive_inframe_deletion	Exon 1 of 4		XP_006719257.1	O95390A0A024RB20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GDF11	ENST00000257868.10 link	c.114_116delGGC	p.Ala39del	disruptive_inframe_deletion	Exon 1 of 3	1	NM_005811.5	ENSP00000257868.5		O95390
GDF11	ENST00000546799.1 link	c.30_32delGGC	p.Ala11del	disruptive_inframe_deletion	Exon 1 of 4	1		ENSP00000448390.1		H0YI30

Frequencies

GnomAD3 genomes

AF:

0.00111

AC:

162

AN:

145650

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00352

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000747

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.000240

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000610

Gnomad OTH

AF:

0.000497

GnomAD3 exomes

AF:

0.00230

AC:

AN:

434

Hom.:

AF XY:

0.00

AC XY:

AN XY:

238

show subpopulations

Gnomad FIN exome

AF:

0.00980

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00799

AC:

6552

AN:

819642

Hom.:

AF XY:

0.00820

AC XY:

3122

AN XY:

380906

show subpopulations

Gnomad4 AFR exome

AF:

0.0129

Gnomad4 AMR exome

AF:

0.0214

Gnomad4 ASJ exome

AF:

0.00938

Gnomad4 EAS exome

AF:

0.0125

Gnomad4 SAS exome

AF:

0.00785

Gnomad4 FIN exome

AF:

0.0344

Gnomad4 NFE exome

AF:

0.00778

Gnomad4 OTH exome

AF:

0.00816

GnomAD4 genome

AF:

0.00112

AC:

163

AN:

145750

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

AN XY:

70864

show subpopulations

Gnomad4 AFR

AF:

0.00354

Gnomad4 AMR

AF:

0.000746

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000210

Gnomad4 FIN

AF:

0.000240

Gnomad4 NFE

AF:

0.0000610

Gnomad4 OTH

AF:

0.000491

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

GDF11-related disorder

Benign:1

Feb 08, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over