rs4678523

Positions:

• chr3-32996229-T-C

Variant summary

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

The NM_001393580.1(GLB1):​c.1734+17827A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 152,034 control chromosomes in the GnomAD database, including 6,752 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 0.29 (6752 hom., cov: 33)
• Consequence: GLB1 NM_001393580.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.58

Genes affected

GLB1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLB1	NM_001393580.1	c.1734+17827A>G		intron_variant			NP_001380509.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43770 AN: 151916 Hom.: 6749 Cov.: 33

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.325

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.288 AC: 43807 AN: 152034 Hom.: 6752 Cov.: 33 AF XY: 0.287 AC XY: 21287 AN XY: 74296

Gnomad4 AFR AF: 0.227

Gnomad4 AMR AF: 0.370

Gnomad4 ASJ AF: 0.428

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.264

Gnomad4 NFE AF: 0.314

Gnomad4 OTH AF: 0.321

Alfa AF: 0.326 Hom.: 8707

Bravo AF: 0.295

Asia WGS AF: 0.182 AC: 636 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.036
DANN	Benign	0.44

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4678523; hg19: chr3-33037721;