3-32106479-CGGGCCTGGAGGCCGGCCG-C

Variant names:

• chr3-32106479-CGGGCCTGGAGGCCGGCCG-C
• rs199516859
• ENST00000429432.5:c.-71+651_-71+668delGGGCCTGGAGGCCGGCCG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000429432.5(GPD1L):​c.-71+651_-71+668delGGGCCTGGAGGCCGGCCG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0129 in 362,064 control chromosomes in the GnomAD database, including 204 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.025 (175 hom., cov: 32)
  • Exomes 𝑓: 0.0040 (29 hom.)
• Consequence: GPD1L ENST00000429432.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.284
• Publications: 0 publications found

Genes affected

GPD1L (HGNC:28956): (glycerol-3-phosphate dehydrogenase 1 like) The protein encoded by this gene catalyzes the conversion of sn-glycerol 3-phosphate to glycerone phosphate. The encoded protein is found in the cytoplasm, associated with the plasma membrane, where it binds the sodium channel, voltage-gated, type V, alpha subunit (SCN5A). Defects in this gene are a cause of Brugada syndrome type 2 (BRS2) as well as sudden infant death syndrome (SIDS). [provided by RefSeq, Jul 2010]

GPD1L Gene-Disease associations (from GenCC):

• Brugada syndrome 2

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• Brugada syndrome 1

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 3-32106479-CGGGCCTGGAGGCCGGCCG-C is Benign according to our data. Variant chr3-32106479-CGGGCCTGGAGGCCGGCCG-C is described in ClinVar as Benign. ClinVar VariationId is 1229730.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0845 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000429432.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPD1L	NM_015141.4	MANE Select	c.-232_-215delGGGCCTGGAGGCCGGCCG		upstream_gene	N/A	NP_055956.1	Q8N335

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPD1L	ENST00000429432.5	TSL:4	c.-71+651_-71+668delGGGCCTGGAGGCCGGCCG		intron	N/A	ENSP00000393861.1	C9K0P5
	GPD1L	ENST00000282541.10	TSL:1 MANE Select	c.-232_-215delGGGCCTGGAGGCCGGCCG		upstream_gene	N/A	ENSP00000282541.6	Q8N335
	GPD1L	ENST00000902849.1		c.-232_-215delGGGCCTGGAGGCCGGCCG		upstream_gene	N/A	ENSP00000572908.1

Frequencies

GnomAD3 genomes AF: 0.0252 AC: 3834 AN: 152078 Hom.: 174 Cov.: 32

Gnomad AFR AF: 0.0870

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00903

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.000603

Gnomad OTH AF: 0.0211

GnomAD4 exome AF: 0.00404 AC: 848 AN: 209878 Hom.: 29 AF XY: 0.00354 AC XY: 381 AN XY: 107542

African (AFR) AF: 0.0947 AC: 554 AN: 5850

American (AMR) AF: 0.00924 AC: 55 AN: 5952

Ashkenazi Jewish (ASJ) AF: 0.000409 AC: 3 AN: 7338

East Asian (EAS) AF: 0.00 AC: 0 AN: 19040

South Asian (SAS) AF: 0.00 AC: 0 AN: 2100

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 18930

Middle Eastern (MID) AF: 0.00464 AC: 5 AN: 1078

European-Non Finnish (NFE) AF: 0.000676 AC: 92 AN: 136138

Other (OTH) AF: 0.0103 AC: 139 AN: 13452

GnomAD4 genome AF: 0.0252 AC: 3839 AN: 152186 Hom.: 175 Cov.: 32 AF XY: 0.0241 AC XY: 1793 AN XY: 74408

African (AFR) AF: 0.0869 AC: 3608 AN: 41526

American (AMR) AF: 0.00901 AC: 138 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5144

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.0137 AC: 4 AN: 292

European-Non Finnish (NFE) AF: 0.000603 AC: 41 AN: 67976

Other (OTH) AF: 0.0208 AC: 44 AN: 2112

Alfa AF: 0.0232 Hom.: 6

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.28

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs199516859; hg19: chr3-32147971;