chr1-235341998-A-AT

Position:

• chr1-235341998-A-AT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_004837.4(GGPS1):​c.142-6dup variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 1,463,350 control chromosomes in the GnomAD database, including 89,021 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.32 (8231 hom., cov: 0)
  • Exomes 𝑓: 0.35 (80790 hom.)
• Consequence: GGPS1 NM_004837.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.25

Genes affected

GGPS1 (HGNC:4249): (geranylgeranyl diphosphate synthase 1) This gene is a member of the prenyltransferase family and encodes a protein with geranylgeranyl diphosphate (GGPP) synthase activity. The enzyme catalyzes the synthesis of GGPP from farnesyl diphosphate and isopentenyl diphosphate. GGPP is an important molecule responsible for the C20-prenylation of proteins and for the regulation of a nuclear hormone receptor. Alternate transcriptional splice variants, both protein-coding and non-protein-coding, have been found for this gene. [provided by RefSeq, Sep 2010]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GGPS1	NM_004837.4	c.142-6dup		splice_polypyrimidine_tract_variant, intron_variant		ENST00000282841.9	NP_004828.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GGPS1	ENST00000282841.9	c.142-6dup		splice_polypyrimidine_tract_variant, intron_variant		1	NM_004837.4	ENSP00000282841	P1

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48836 AN: 151818 Hom.: 8217 Cov.: 0

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.306

GnomAD3 exomes AF: 0.341 AC: 64550 AN: 189418 Hom.: 11448 AF XY: 0.348 AC XY: 35880 AN XY: 103060

Gnomad AFR exome AF: 0.254

Gnomad AMR exome AF: 0.342

Gnomad ASJ exome AF: 0.281

Gnomad EAS exome AF: 0.228

Gnomad SAS exome AF: 0.511

Gnomad FIN exome AF: 0.370

Gnomad NFE exome AF: 0.335

Gnomad OTH exome AF: 0.326

GnomAD4 exome AF: 0.345 AC: 452814 AN: 1311414 Hom.: 80790 Cov.: 21 AF XY: 0.351 AC XY: 229181 AN XY: 653020

Gnomad4 AFR exome AF: 0.241

Gnomad4 AMR exome AF: 0.330

Gnomad4 ASJ exome AF: 0.284

Gnomad4 EAS exome AF: 0.261

Gnomad4 SAS exome AF: 0.515

Gnomad4 FIN exome AF: 0.374

Gnomad4 NFE exome AF: 0.340

Gnomad4 OTH exome AF: 0.337

GnomAD4 genome AF: 0.322 AC: 48878 AN: 151936 Hom.: 8231 Cov.: 0 AF XY: 0.328 AC XY: 24373 AN XY: 74254

Gnomad4 AFR AF: 0.260

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.287

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.525

Gnomad4 FIN AF: 0.374

Gnomad4 NFE AF: 0.347

Gnomad4 OTH AF: 0.301

Asia WGS AF: 0.362 AC: 1255 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs3841735; hg19: chr1-235505313;