rs4514547

Positions:

• chr13-39664762-C-T

Variant summary

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

The NM_020751.3(COG6):​c.370-334C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 152,120 control chromosomes in the GnomAD database, including 33,470 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 0.66 (33470 hom., cov: 33)
• Consequence: COG6 NM_020751.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.247

Genes affected

COG6 (HGNC:18621): (component of oligomeric golgi complex 6) This gene encodes a subunit of the conserved oligomeric Golgi complex that is required for maintaining normal structure and activity of the Golgi apparatus. The encoded protein is organized with conserved oligomeric Golgi complex components 5, 7 and 8 into a sub-complex referred to as lobe B. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Feb 2009]

COG6 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COG6	NM_020751.3	c.370-334C>T		intron_variant		ENST00000455146.8	NP_065802.1
COG6	NM_001145079.2	c.370-334C>T		intron_variant			NP_001138551.1
COG6	XM_011535168.2	c.370-334C>T		intron_variant			XP_011533470.1
COG6	NR_026745.1	n.535-334C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COG6	ENST00000455146.8	c.370-334C>T		intron_variant		1	NM_020751.3	ENSP00000397441.2

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100485 AN: 152002 Hom.: 33440 Cov.: 33

Gnomad AFR AF: 0.602

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.771

Gnomad ASJ AF: 0.775

Gnomad EAS AF: 0.714

Gnomad SAS AF: 0.687

Gnomad FIN AF: 0.645

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.661

Gnomad OTH AF: 0.685

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

GnomAD4 genome AF: 0.661 AC: 100569 AN: 152120 Hom.: 33470 Cov.: 33 AF XY: 0.663 AC XY: 49346 AN XY: 74378

Gnomad4 AFR AF: 0.601

Gnomad4 AMR AF: 0.771

Gnomad4 ASJ AF: 0.775

Gnomad4 EAS AF: 0.714

Gnomad4 SAS AF: 0.689

Gnomad4 FIN AF: 0.645

Gnomad4 NFE AF: 0.661

Gnomad4 OTH AF: 0.688

Alfa AF: 0.673 Hom.: 42555

Bravo AF: 0.670

Asia WGS AF: 0.690 AC: 2400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.35

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: rs4514547; hg19: chr13-40238899;