rs3732410

Positions:

• chr3-121696873-T-C
• chr3-121696873-T-G

Variant summary

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

The NM_001366282.2(GOLGB1):​c.3650A>G​(p.Tyr1217Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 1,613,820 control chromosomes in the GnomAD database, including 44,756 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 0.20 (3651 hom., cov: 32)
  • Exomes 𝑓: 0.23 (41105 hom.)
• Consequence: GOLGB1 NM_001366282.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.95

Genes affected

GOLGB1 (HGNC:4429): (golgin B1) Enables RNA binding activity. Involved in protein localization to pericentriolar material. Located in Golgi apparatus and endoplasmic reticulum-Golgi intermediate compartment. [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 (MetaRNN=0.002850145).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GOLGB1	NM_001366282.2	c.3650A>G	p.Tyr1217Cys	missense_variant	13/22	ENST00000614479.5	NP_001353211.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GOLGB1	ENST00000614479.5	c.3650A>G	p.Tyr1217Cys	missense_variant	13/22	1	NM_001366282.2	ENSP00000484083	P3

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30212 AN: 152080 Hom.: 3652 Cov.: 32

Gnomad AFR AF: 0.0774

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.237

GnomAD3 exomes AF: 0.231 AC: 58132 AN: 251292 Hom.: 7800 AF XY: 0.237 AC XY: 32174 AN XY: 135808

Gnomad AFR exome AF: 0.0701

Gnomad AMR exome AF: 0.140

Gnomad ASJ exome AF: 0.288

Gnomad EAS exome AF: 0.479

Gnomad SAS exome AF: 0.218

Gnomad FIN exome AF: 0.207

Gnomad NFE exome AF: 0.244

Gnomad OTH exome AF: 0.253

GnomAD4 exome AF: 0.231 AC: 337776 AN: 1461620 Hom.: 41105 Cov.: 36 AF XY: 0.232 AC XY: 168557 AN XY: 727138

Gnomad4 AFR exome AF: 0.0712

Gnomad4 AMR exome AF: 0.146

Gnomad4 ASJ exome AF: 0.289

Gnomad4 EAS exome AF: 0.410

Gnomad4 SAS exome AF: 0.222

Gnomad4 FIN exome AF: 0.212

Gnomad4 NFE exome AF: 0.232

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.199 AC: 30216 AN: 152200 Hom.: 3651 Cov.: 32 AF XY: 0.198 AC XY: 14711 AN XY: 74416

Gnomad4 AFR AF: 0.0776

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.290

Gnomad4 EAS AF: 0.461

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.213

Gnomad4 NFE AF: 0.244

Gnomad4 OTH AF: 0.235

Alfa AF: 0.240 Hom.: 11586

Bravo AF: 0.196

TwinsUK AF: 0.224 AC: 830

ALSPAC AF: 0.223 AC: 861

ESP6500AA AF: 0.0742 AC: 327

ESP6500EA AF: 0.246 AC: 2113

ExAC AF: 0.231 AC: 28046

Asia WGS AF: 0.286 AC: 993 AN: 3478

EpiCase AF: 0.248

EpiControl AF: 0.256

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T;.;.;.
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.84	T;T;T;T
MetaRNN	Benign	0.0029	T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.1	M;.;.;.
MutationTaster	Benign	0.15	P;P
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.2	D;D;.;D
REVEL	Benign	0.12
Sift	Benign	0.077	T;T;.;T
Sift4G	Uncertain	0.013	D;D;D;.
Polyphen		1.0	D;.;.;P
Vest4		0.29
MPC		0.18
ClinPred		0.031	T
GERP RS		4.6
Varity_R		0.17
gMVP		0.47

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: rs3732410; hg19: chr3-121415720; COSMIC: COSV61467407; COSMIC: COSV61467407;