rs1060504781

Variant names:

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_001492.6(GDF1):c.537G>A(p.Gly179Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000284 in 1,161,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000034 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

GDF1
NM_001492.6 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.504

Publications

0 publications found

Variant links:

Genes affected

GDF1 (HGNC:4214): (growth differentiation factor 1) 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. Studies in rodents suggest that this protein is involved in the establishment of left-right asymmetry in early embryogenesis and in neural development in later embryogenesis. The encoded protein is translated from a bicistronic mRNA that also encodes ceramide synthase 1. Mutations in this gene are associated with several congenital cardiovascular malformations. [provided by RefSeq, Jul 2016]

GDF1 links:

CERS1 (HGNC:14253): (ceramide synthase 1) This gene encodes a ceramide synthase enzyme, which catalyzes the synthesis of ceramide, the hydrophobic moiety of sphingolipids. The encoded enzyme synthesizes 18-carbon (C18) ceramide in brain neurons. Elevated expression of this gene may be associated with increased longevity, while decreased expression of this gene may be associated with myoclonus epilepsy with dementia in human patients. This protein is transcribed from a monocistronic mRNA as well as a bicistronic mRNA, which also encodes growth differentiation factor 1. [provided by RefSeq, Jul 2016]

CERS1 Gene-Disease associations (from GenCC):

progressive myoclonic epilepsy type 8
Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

CERS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 19-18869179-C-T is Benign according to our data. Variant chr19-18869179-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 416262.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.504 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
GDF1	NM_001492.6 link	c.537G>A	p.Gly179Gly	synonymous_variant	Exon 8 of 8	ENST00000247005.8	NP_001483.3
CERS1	NM_021267.5 link	c.*806G>A		3_prime_UTR_variant	Exon 8 of 8	ENST00000623882.4	NP_067090.1
GDF1	NM_001387438.1 link	c.537G>A	p.Gly179Gly	synonymous_variant	Exon 5 of 5		NP_001374367.1
CERS1	NM_001387440.1 link	c.*1398G>A		3_prime_UTR_variant	Exon 7 of 7		NP_001374369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GDF1	ENST00000247005.8 link	c.537G>A	p.Gly179Gly	synonymous_variant	Exon 8 of 8	1	NM_001492.6	ENSP00000247005.5
CERS1	ENST00000623882.4 link	c.*806G>A		3_prime_UTR_variant	Exon 8 of 8	1	NM_021267.5	ENSP00000485308.1

Frequencies

GnomAD3 genomes

AF:

0.0000269

AC:

AN:

148458

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000601

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00160

AC:

AN:

626

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00230

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000276

AC:

AN:

1013376

Hom.:

Cov.:

AF XY:

0.0000310

AC XY:

AN XY:

483372

show subpopulations

African (AFR)

AF:

0.0000513

AC:

AN:

19492

American (AMR)

AF:

0.00

AC:

AN:

5562

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10274

East Asian (EAS)

AF:

0.00

AC:

AN:

16528

South Asian (SAS)

AF:

0.00

AC:

AN:

25518

European-Finnish (FIN)

AF:

0.00

AC:

AN:

17900

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2460

European-Non Finnish (NFE)

AF:

0.0000296

AC:

AN:

877828

Other (OTH)

AF:

0.0000264

AC:

AN:

37814

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000337

AC:

AN:

148566

Hom.:

Cov.:

AF XY:

0.0000414

AC XY:

AN XY:

72440

show subpopulations

African (AFR)

AF:

0.0000243

AC:

AN:

41214

American (AMR)

AF:

0.00

AC:

AN:

14960

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3402

East Asian (EAS)

AF:

0.00

AC:

AN:

5132

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9196

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000601

AC:

AN:

66566

Other (OTH)

AF:

0.00

AC:

AN:

2064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000712

Hom.:

Bravo

AF:

0.0000416

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 15, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

4.1

(source)

DANN

Benign

0.97

PhyloP100

-0.50

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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over