rs328406

Positions:

• chr19-34348093-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014686.5(GARRE1):​c.2687+51C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 1,363,960 control chromosomes in the GnomAD database, including 41,916 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.22 (4427 hom., cov: 32)
  • Exomes 𝑓: 0.24 (37489 hom.)
• Consequence: GARRE1 NM_014686.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.746

Genes affected

GARRE1 (HGNC:29016): (granule associated Rac and RHOG effector 1) Enables CCR4-NOT complex binding activity and small GTPase binding activity. Involved in Rac protein signal transduction. Located in P-body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GARRE1	NM_014686.5	c.2687+51C>T		intron_variant		ENST00000299505.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GARRE1	ENST00000299505.8	c.2687+51C>T		intron_variant		1	NM_014686.5	P1
GARRE1	ENST00000588338.6	n.264-1027C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34186 AN: 152034 Hom.: 4424 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.217

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.617

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.225

GnomAD3 exomes AF: 0.254 AC: 29028 AN: 114466 Hom.: 4190 AF XY: 0.251 AC XY: 15532 AN XY: 61836

Gnomad AFR exome AF: 0.179

Gnomad AMR exome AF: 0.239

Gnomad ASJ exome AF: 0.218

Gnomad EAS exome AF: 0.624

Gnomad SAS exome AF: 0.207

Gnomad FIN exome AF: 0.258

Gnomad NFE exome AF: 0.226

Gnomad OTH exome AF: 0.235

GnomAD4 exome AF: 0.238 AC: 288080 AN: 1211806 Hom.: 37489 Cov.: 23 AF XY: 0.237 AC XY: 139199 AN XY: 587356

Gnomad4 AFR exome AF: 0.171

Gnomad4 AMR exome AF: 0.222

Gnomad4 ASJ exome AF: 0.210

Gnomad4 EAS exome AF: 0.663

Gnomad4 SAS exome AF: 0.205

Gnomad4 FIN exome AF: 0.255

Gnomad4 NFE exome AF: 0.227

Gnomad4 OTH exome AF: 0.249

GnomAD4 genome AF: 0.225 AC: 34198 AN: 152154 Hom.: 4427 Cov.: 32 AF XY: 0.227 AC XY: 16877 AN XY: 74432

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.618

Gnomad4 SAS AF: 0.214

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.224

Alfa AF: 0.233 Hom.: 660

Bravo AF: 0.221

Asia WGS AF: 0.380 AC: 1321 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.68
DANN	Benign	0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs328406; hg19: chr19-34838998;