Variant 19-18869245-T-TGCCGCCGCC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP3

The NM_001492.6(GDF1):c.462_470dupGGCGGCGGC(p.Ala155_Ala157dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000231 in 1,428,204 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

GDF1
NM_001492.6 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.179

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001492.6

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GDF1	NM_001492.6 linkuse as main transcript	c.462_470dupGGCGGCGGC	p.Ala155_Ala157dup	disruptive_inframe_insertion	8/8	ENST00000247005.8	NP_001483.3	P27539A0A024R7N8
CERS1	NM_021267.5 linkuse as main transcript	c.731_739dupGGCGGCGGC		3_prime_UTR_variant	8/8	ENST00000623882.4	NP_067090.1	P27544-1
GDF1	NM_001387438.1 linkuse as main transcript	c.462_470dupGGCGGCGGC	p.Ala155_Ala157dup	disruptive_inframe_insertion	5/5		NP_001374367.1
CERS1	NM_001387440.1 linkuse as main transcript	c.1323_1331dupGGCGGCGGC		3_prime_UTR_variant	7/7		NP_001374369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GDF1	ENST00000247005.8 linkuse as main transcript	c.462_470dupGGCGGCGGC	p.Ala155_Ala157dup	disruptive_inframe_insertion	8/8	1	NM_001492.6	ENSP00000247005.5		P27539
CERS1	ENST00000623882 linkuse as main transcript	c.731_739dupGGCGGCGGC		3_prime_UTR_variant	8/8	1	NM_021267.5	ENSP00000485308.1		P27544-1

Frequencies

GnomAD3 genomes

AF:

0.0000199

AC:

AN:

150516

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000485

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:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000235

AC:

AN:

1277688

Hom.:

Cov.:

AF XY:

0.0000255

AC XY:

AN XY:

627912

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000156

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000280

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000199

AC:

AN:

150516

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73502

show subpopulations

Gnomad4 AFR

AF:

0.0000485

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over