rs80034177

Variant names:

• chr16-70500950-G-A
• rs80034177
• NM_015386.3:c.1195+8C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-70500950-G-A
• chr16-70500950-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015386.3(COG4):​c.1195+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00594 in 1,613,914 control chromosomes in the GnomAD database, including 520 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.032 (284 hom., cov: 31)
  • Exomes 𝑓: 0.0033 (236 hom.)
• Consequence: COG4 NM_015386.3 splice_region, intron
• Scores: Splicing: ADA: 0.00004054
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.613
• Publications: 1 publications found

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]

COG4 Gene-Disease associations (from GenCC):

• COG4-congenital disorder of glycosylation

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P, ClinGen
• microcephalic osteodysplastic dysplasia, Saul-Wilson type

  Inheritance: AD, AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 16-70500950-G-A is Benign according to our data. Variant chr16-70500950-G-A is described in ClinVar as Benign. ClinVar VariationId is 320375.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015386.3. 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
	COG4	NM_015386.3	MANE Select	c.1195+8C>T		splice_region intron	N/A	NP_056201.2	J3KNI1
	COG4	NM_001195139.2		c.1183+8C>T		splice_region intron	N/A	NP_001182068.2	A0A6I8PIQ6
	COG4	NM_001365426.1		c.769+8C>T		splice_region intron	N/A	NP_001352355.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG4	ENST00000323786.10	TSL:1 MANE Select	c.1195+8C>T		splice_region intron	N/A	ENSP00000315775.5	J3KNI1
	COG4	ENST00000393612.8	TSL:1	c.1195+8C>T		splice_region intron	N/A	ENSP00000377236.5	A0A0A0MS45
	COG4	ENST00000530314.5	TSL:1	n.1874+8C>T		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0317 AC: 4822 AN: 152080 Hom.: 284 Cov.: 31

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.0244

GnomAD2 exomes AF: 0.00792 AC: 1991 AN: 251408 AF XY: 0.00617

Gnomad AFR exome AF: 0.108

Gnomad AMR exome AF: 0.00382

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000290

Gnomad OTH exome AF: 0.00521

GnomAD4 exome AF: 0.00326 AC: 4769 AN: 1461716 Hom.: 236 Cov.: 31 AF XY: 0.00292 AC XY: 2125 AN XY: 727172

African (AFR) AF: 0.112 AC: 3755 AN: 33474

American (AMR) AF: 0.00436 AC: 195 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39690

South Asian (SAS) AF: 0.00174 AC: 150 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53314

Middle Eastern (MID) AF: 0.00243 AC: 14 AN: 5768

European-Non Finnish (NFE) AF: 0.000194 AC: 216 AN: 1111962

Other (OTH) AF: 0.00719 AC: 434 AN: 60394

GnomAD4 genome AF: 0.0317 AC: 4825 AN: 152198 Hom.: 284 Cov.: 31 AF XY: 0.0309 AC XY: 2302 AN XY: 74408

African (AFR) AF: 0.110 AC: 4563 AN: 41496

American (AMR) AF: 0.0111 AC: 169 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000426 AC: 29 AN: 68028

Other (OTH) AF: 0.0265 AC: 56 AN: 2114

Alfa AF: 0.0148 Hom.: 83

Bravo AF: 0.0350

Asia WGS AF: 0.0180 AC: 61 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	COG4-congenital disorder of glycosylation (1)
-	-	1	COG4-related disorder (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.78
DANN	Benign	0.38
PhyloP100		-0.61
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000041
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.010		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: rs80034177; hg19: chr16-70534853;