rs722579

Positions:

• chr16-70494321-C-T

Variant summary

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

The ENST00000323786.10(COG4):​c.1647+1945G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 151,948 control chromosomes in the GnomAD database, including 12,624 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 0.40 (12624 hom., cov: 32)
• Consequence: COG4 ENST00000323786.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.774

Genes affected

COG4 (HGNC:18620): (component of oligomeric golgi complex 4) The protein encoded by this gene is a component of an oligomeric protein complex involved in the structure and function of the Golgi apparatus. Defects in this gene may be a cause of congenital disorder of glycosylation type IIj. Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Aug 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.64 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COG4	NM_015386.3	c.1647+1945G>A		intron_variant		ENST00000323786.10	NP_056201.2
COG4	NM_001195139.2	c.1635+1945G>A		intron_variant			NP_001182068.2
COG4	NM_001365426.1	c.1221+1945G>A		intron_variant			NP_001352355.1
COG4	NR_158212.1	n.1606+1945G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COG4	ENST00000323786.10	c.1647+1945G>A		intron_variant		1	NM_015386.3	ENSP00000315775	P1

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60654 AN: 151830 Hom.: 12615 Cov.: 32

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.658

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.426

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

GnomAD4 genome AF: 0.399 AC: 60686 AN: 151948 Hom.: 12624 Cov.: 32 AF XY: 0.404 AC XY: 29982 AN XY: 74232

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.450

Gnomad4 ASJ AF: 0.427

Gnomad4 EAS AF: 0.577

Gnomad4 SAS AF: 0.659

Gnomad4 FIN AF: 0.351

Gnomad4 NFE AF: 0.420

Gnomad4 OTH AF: 0.427

Alfa AF: 0.424 Hom.: 13643

Bravo AF: 0.400

Asia WGS AF: 0.625 AC: 2174 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	15
DANN	Benign	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: rs722579; hg19: chr16-70528224;