3-121696873-T-C

Variant names:

• chr3-121696873-T-C
• rs3732410
• NM_001366282.2:c.3650A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 46 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366282.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLGB1	NM_001366282.2	MANE Select	c.3650A>G	p.Tyr1217Cys	missense	Exon 13 of 22	NP_001353211.1
	GOLGB1	NM_001256486.2		c.3650A>G	p.Tyr1217Cys	missense	Exon 13 of 22	NP_001243415.1
	GOLGB1	NM_004487.5		c.3635A>G	p.Tyr1212Cys	missense	Exon 13 of 22	NP_004478.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLGB1	ENST00000614479.5	TSL:1 MANE Select	c.3650A>G	p.Tyr1217Cys	missense	Exon 13 of 22	ENSP00000484083.2
	GOLGB1	ENST00000393667.8	TSL:1	c.3650A>G	p.Tyr1217Cys	missense	Exon 13 of 22	ENSP00000377275.3
	GOLGB1	ENST00000340645.10	TSL:1	c.3635A>G	p.Tyr1212Cys	missense	Exon 13 of 22	ENSP00000341848.5

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

GnomAD2 exomes AF: 0.231 AC: 58132 AN: 251292 AF XY: 0.237

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 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

African (AFR) AF: 0.0712 AC: 2382 AN: 33470

American (AMR) AF: 0.146 AC: 6549 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 7551 AN: 26134

East Asian (EAS) AF: 0.410 AC: 16292 AN: 39698

South Asian (SAS) AF: 0.222 AC: 19178 AN: 86248

European-Finnish (FIN) AF: 0.212 AC: 11322 AN: 53414

Middle Eastern (MID) AF: 0.309 AC: 1785 AN: 5768

European-Non Finnish (NFE) AF: 0.232 AC: 257627 AN: 1111786

Other (OTH) AF: 0.250 AC: 15090 AN: 60378

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

African (AFR) AF: 0.0776 AC: 3225 AN: 41556

American (AMR) AF: 0.194 AC: 2964 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 1005 AN: 3466

East Asian (EAS) AF: 0.461 AC: 2381 AN: 5166

South Asian (SAS) AF: 0.210 AC: 1012 AN: 4828

European-Finnish (FIN) AF: 0.213 AC: 2256 AN: 10578

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.244 AC: 16567 AN: 67998

Other (OTH) AF: 0.235 AC: 495 AN: 2108

Alfa AF: 0.236 Hom.: 15107

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 v4.9

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
MetaRNN	Benign	0.0029	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.9
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.12
Sift	Benign	0.077	T
Sift4G	Uncertain	0.013	D
Polyphen		1.0	D
Vest4		0.29
MPC		0.18
ClinPred		0.031	T
GERP RS		4.6
Varity_R		0.17
gMVP		0.47
Mutation Taster		=96/4	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: rs3732410; hg19: chr3-121415720; COSMIC: COSV61467407; COSMIC: COSV61467407;