rs6971091

Positions:

• chr7-128723233-G-A

Variant summary

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

The NM_001282788.3(GARIN1B):​c.724G>A​(p.Glu242Lys) variant causes a missense change. The variant allele was found at a frequency of 0.218 in 1,611,952 control chromosomes in the GnomAD database, including 40,350 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.18 (2823 hom., cov: 31)
  • Exomes 𝑓: 0.22 (37527 hom.)
• Consequence: GARIN1B NM_001282788.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.07

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016109645).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GARIN1B	NM_001282788.3	c.724G>A	p.Glu242Lys	missense_variant	4/7	ENST00000621392.5	NP_001269717.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GARIN1B	ENST00000621392.5	c.724G>A	p.Glu242Lys	missense_variant	4/7	5	NM_001282788.3	ENSP00000477573.2

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27537 AN: 151920 Hom.: 2822 Cov.: 31

Gnomad AFR AF: 0.0835

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.186

GnomAD3 exomes AF: 0.202 AC: 50665 AN: 251332 Hom.: 5747 AF XY: 0.210 AC XY: 28544 AN XY: 135826

Gnomad AFR exome AF: 0.0794

Gnomad AMR exome AF: 0.116

Gnomad ASJ exome AF: 0.188

Gnomad EAS exome AF: 0.113

Gnomad SAS exome AF: 0.287

Gnomad FIN exome AF: 0.239

Gnomad NFE exome AF: 0.231

Gnomad OTH exome AF: 0.192

GnomAD4 exome AF: 0.222 AC: 323988 AN: 1459914 Hom.: 37527 Cov.: 32 AF XY: 0.225 AC XY: 163056 AN XY: 726268

Gnomad4 AFR exome AF: 0.0797

Gnomad4 AMR exome AF: 0.120

Gnomad4 ASJ exome AF: 0.187

Gnomad4 EAS exome AF: 0.122

Gnomad4 SAS exome AF: 0.286

Gnomad4 FIN exome AF: 0.238

Gnomad4 NFE exome AF: 0.230

Gnomad4 OTH exome AF: 0.212

GnomAD4 genome AF: 0.181 AC: 27542 AN: 152038 Hom.: 2823 Cov.: 31 AF XY: 0.183 AC XY: 13587 AN XY: 74298

Gnomad4 AFR AF: 0.0833

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.276

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.231

Gnomad4 OTH AF: 0.189

Alfa AF: 0.215 Hom.: 8872

Bravo AF: 0.163

TwinsUK AF: 0.232 AC: 859

ALSPAC AF: 0.219 AC: 844

ESP6500AA AF: 0.0797 AC: 351

ESP6500EA AF: 0.229 AC: 1973

ExAC AF: 0.204 AC: 24748

Asia WGS AF: 0.202 AC: 703 AN: 3478

EpiCase AF: 0.225

EpiControl AF: 0.218

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0094	.;.;T;.
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.86	.;D;T;T
MetaRNN	Benign	0.0016	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	.;.;L;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-3.1	D;.;N;N
REVEL	Benign	0.11
Sift	Uncertain	0.0070	D;.;D;D
Sift4G	Uncertain	0.011	D;D;D;D
Polyphen		0.92	.;.;P;.
Vest4		0.12
MPC		0.48
ClinPred		0.025	T
GERP RS		5.2
Varity_R		0.15
gMVP		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs6971091; hg19: chr7-128363287; COSMIC: COSV59373294; COSMIC: COSV59373294;