rs2985981

Variant names:

• chr13-45520527-A-G
• rs2985981
• NM_031431.4:c.2154+1433A>G

Your query was ambiguous. Multiple possible variants found:

• chr13-45520527-A-G
• chr13-45520527-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031431.4(COG3):​c.2154+1433A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.723 in 152,006 control chromosomes in the GnomAD database, including 41,269 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 0.72 (41269 hom., cov: 31)
• Consequence: COG3 NM_031431.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.438
• Publications: 2 publications found

Genes affected

COG3 (HGNC:18619): (component of oligomeric golgi complex 3) This gene encodes a component of the conserved oligomeric Golgi (COG) complex which is composed of eight different subunits and is required for normal Golgi morphology and localization. Defects in the COG complex result in multiple deficiencies in protein glycosylation. The protein encoded by this gene is involved in ER-Golgi transport.[provided by RefSeq, Jun 2011]

COG3 Gene-Disease associations (from GenCC):

• congenital disorder of glycosylation, type IIbb

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COG3	NM_031431.4	c.2154+1433A>G		intron_variant	Intron 19 of 22	ENST00000349995.10	NP_113619.3
COG3	XM_047430702.1	c.1930+4264A>G		intron_variant	Intron 17 of 18		XP_047286658.1
COG3	XR_429222.5	n.2252+1433A>G		intron_variant	Intron 19 of 23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COG3	ENST00000349995.10	c.2154+1433A>G		intron_variant	Intron 19 of 22	1	NM_031431.4	ENSP00000258654.8
COG3	ENST00000486940.2	n.115+4264A>G		intron_variant	Intron 1 of 5	2		ENSP00000477882.1

Frequencies

GnomAD3 genomes AF: 0.723 AC: 109849 AN: 151888 Hom.: 41254 Cov.: 31

Gnomad AFR AF: 0.506

Gnomad AMI AF: 0.908

Gnomad AMR AF: 0.821

Gnomad ASJ AF: 0.814

Gnomad EAS AF: 0.759

Gnomad SAS AF: 0.803

Gnomad FIN AF: 0.726

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.816

Gnomad OTH AF: 0.759

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

GnomAD4 genome AF: 0.723 AC: 109908 AN: 152006 Hom.: 41269 Cov.: 31 AF XY: 0.725 AC XY: 53844 AN XY: 74282

African (AFR) AF: 0.506 AC: 20985 AN: 41436

American (AMR) AF: 0.821 AC: 12540 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.814 AC: 2826 AN: 3472

East Asian (EAS) AF: 0.759 AC: 3929 AN: 5178

South Asian (SAS) AF: 0.803 AC: 3871 AN: 4818

European-Finnish (FIN) AF: 0.726 AC: 7641 AN: 10522

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.815 AC: 55443 AN: 67988

Other (OTH) AF: 0.760 AC: 1605 AN: 2112

Alfa AF: 0.786 Hom.: 21181

Bravo AF: 0.721

Asia WGS AF: 0.783 AC: 2714 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.9
DANN	Benign	0.30
PhyloP100		-0.44
Mutation Taster		=100/0	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: rs2985981; hg19: chr13-46094662;