rs745229

Variant names:

• chr7-128718837-C-A
• rs745229
• NM_001282788.3:c.441C>A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001282788.3(GARIN1B):​c.441C>A​(p.Leu147Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 1,613,088 control chromosomes in the GnomAD database, including 42,528 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 (3655 hom., cov: 31)
  • Exomes 𝑓: 0.23 (38873 hom.)
• Consequence: GARIN1B NM_001282788.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.496

Genes affected

GARIN1B (HGNC:30704): (golgi associated RAB2 interactor 1B)

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BP7: Synonymous conserved (PhyloP=0.496 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GARIN1B	NM_001282788.3	c.441C>A	p.Leu147Leu	synonymous_variant	Exon 3 of 7	ENST00000621392.5	NP_001269717.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GARIN1B	ENST00000621392.5	c.441C>A	p.Leu147Leu	synonymous_variant	Exon 3 of 7	5	NM_001282788.3	ENSP00000477573.2

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33192 AN: 151986 Hom.: 3649 Cov.: 31

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.213

GnomAD3 exomes AF: 0.211 AC: 52932 AN: 250356 Hom.: 6096 AF XY: 0.217 AC XY: 29431 AN XY: 135338

Gnomad AFR exome AF: 0.214

Gnomad AMR exome AF: 0.116

Gnomad ASJ exome AF: 0.190

Gnomad EAS exome AF: 0.114

Gnomad SAS exome AF: 0.286

Gnomad FIN exome AF: 0.242

Gnomad NFE exome AF: 0.233

Gnomad OTH exome AF: 0.200

GnomAD4 exome AF: 0.227 AC: 332064 AN: 1460984 Hom.: 38873 Cov.: 35 AF XY: 0.229 AC XY: 166605 AN XY: 726650

Gnomad4 AFR exome AF: 0.219

Gnomad4 AMR exome AF: 0.120

Gnomad4 ASJ exome AF: 0.189

Gnomad4 EAS exome AF: 0.122

Gnomad4 SAS exome AF: 0.286

Gnomad4 FIN exome AF: 0.241

Gnomad4 NFE exome AF: 0.232

Gnomad4 OTH exome AF: 0.222

GnomAD4 genome AF: 0.218 AC: 33215 AN: 152104 Hom.: 3655 Cov.: 31 AF XY: 0.218 AC XY: 16211 AN XY: 74344

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.191

Gnomad4 EAS AF: 0.114

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.248

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.217

Alfa AF: 0.222 Hom.: 7754

Bravo AF: 0.205

Asia WGS AF: 0.202 AC: 705 AN: 3478

EpiCase AF: 0.226

EpiControl AF: 0.220

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	8.0
DANN	Benign	0.74

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: rs745229; hg19: chr7-128358891; COSMIC: COSV59373938;