rs745229

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282788.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GARIN1B	NM_001282788.3	MANE Select	c.441C>A	p.Leu147Leu	synonymous	Exon 3 of 7	NP_001269717.1
	GARIN1B	NM_032599.4		c.441C>A	p.Leu147Leu	synonymous	Exon 3 of 7	NP_115988.1
	GARIN1B	NR_104242.2		n.492C>A		non_coding_transcript_exon	Exon 3 of 8

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GARIN1B	ENST00000621392.5	TSL:5 MANE Select	c.441C>A	p.Leu147Leu	synonymous	Exon 3 of 7	ENSP00000477573.2
	GARIN1B	ENST00000315184.9	TSL:1	c.441C>A	p.Leu147Leu	synonymous	Exon 3 of 7	ENSP00000326652.4
	GARIN1B	ENST00000471558.5	TSL:1	n.441C>A		non_coding_transcript_exon	Exon 3 of 6	ENSP00000418672.1

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

GnomAD2 exomes AF: 0.211 AC: 52932 AN: 250356 AF XY: 0.217

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 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

African (AFR) AF: 0.219 AC: 7335 AN: 33470

American (AMR) AF: 0.120 AC: 5376 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 4937 AN: 26126

East Asian (EAS) AF: 0.122 AC: 4821 AN: 39674

South Asian (SAS) AF: 0.286 AC: 24655 AN: 86246

European-Finnish (FIN) AF: 0.241 AC: 12855 AN: 53378

Middle Eastern (MID) AF: 0.207 AC: 1193 AN: 5768

European-Non Finnish (NFE) AF: 0.232 AC: 257499 AN: 1111232

Other (OTH) AF: 0.222 AC: 13393 AN: 60378

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

African (AFR) AF: 0.216 AC: 8979 AN: 41494

American (AMR) AF: 0.165 AC: 2518 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 662 AN: 3470

East Asian (EAS) AF: 0.114 AC: 588 AN: 5176

South Asian (SAS) AF: 0.273 AC: 1316 AN: 4828

European-Finnish (FIN) AF: 0.248 AC: 2621 AN: 10562

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.234 AC: 15880 AN: 67972

Other (OTH) AF: 0.217 AC: 458 AN: 2112

Alfa AF: 0.224 Hom.: 16315

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	8.0
DANN	Benign	0.74
PhyloP100		0.50
PromoterAI		0.011	Neutral
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

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