7-107202238-ATCTT-ATCTTTCTT

Variant names:

• chr7-107202238-A-ATCTT
• rs10699573
• NM_006348.5:c.*1274_*1277dupAAGA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_006348.5(COG5):​c.*1274_*1277dupAAGA variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.156 in 152,560 control chromosomes in the GnomAD database, including 2,310 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (2305 hom., cov: 29)
  • Exomes 𝑓: 0.17 (5 hom.)
• Consequence: COG5 NM_006348.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.82
• Publications: 0 publications found

Genes affected

COG5 (HGNC:14857): (component of oligomeric golgi complex 5) The protein encoded by this gene is one of eight proteins (Cog1-8) which form a Golgi-localized complex (COG) required for normal Golgi morphology and function. The encoded protein is organized with conserved oligomeric Golgi complex components 6, 7 and 8 into a sub-complex referred to as lobe B. Alternative splicing results in multiple transcript variants. Mutations in this gene result in congenital disorder of glycosylation type 2I.[provided by RefSeq, Jan 2011]

HBP1 (HGNC:23200): (HMG-box transcription factor 1) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of lipid transport; negative regulation of reactive oxygen species biosynthetic process; and negative regulation of transcription by RNA polymerase II. Located in nuclear speck. Biomarker of osteoarthritis. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 7-107202238-A-ATCTT is Benign according to our data. Variant chr7-107202238-A-ATCTT is described in ClinVar as Likely_benign. ClinVar VariationId is 358437.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006348.5. 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
	COG5	NM_006348.5	MANE Select	c.*1274_*1277dupAAGA		3_prime_UTR	Exon 22 of 22	NP_006339.4
	HBP1	NM_012257.4	MANE Select	c.*809_*812dupCTTT		3_prime_UTR	Exon 11 of 11	NP_036389.2
	COG5	NM_181733.4		c.*1274_*1277dupAAGA		3_prime_UTR	Exon 21 of 21	NP_859422.3	A0AAA9X096

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG5	ENST00000297135.9	TSL:1 MANE Select	c.*1274_*1277dupAAGA		3_prime_UTR	Exon 22 of 22	ENSP00000297135.4	Q9UP83-4
	HBP1	ENST00000222574.9	TSL:1 MANE Select	c.*809_*812dupCTTT		3_prime_UTR	Exon 11 of 11	ENSP00000222574.4	O60381-1
	COG5	ENST00000347053.8	TSL:1	c.*1274_*1277dupAAGA		3_prime_UTR	Exon 21 of 21	ENSP00000334703.3	A0AAA9X096

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23781 AN: 152006 Hom.: 2306 Cov.: 29

Gnomad AFR AF: 0.0431

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.166

GnomAD4 exome AF: 0.165 AC: 72 AN: 436 Hom.: 5 Cov.: 0 AF XY: 0.145 AC XY: 38 AN XY: 262

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.168 AC: 72 AN: 428

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.156 AC: 23778 AN: 152124 Hom.: 2305 Cov.: 29 AF XY: 0.154 AC XY: 11464 AN XY: 74372

African (AFR) AF: 0.0432 AC: 1794 AN: 41560

American (AMR) AF: 0.168 AC: 2575 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 777 AN: 3460

East Asian (EAS) AF: 0.140 AC: 724 AN: 5182

South Asian (SAS) AF: 0.179 AC: 865 AN: 4822

European-Finnish (FIN) AF: 0.169 AC: 1780 AN: 10560

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.216 AC: 14641 AN: 67928

Other (OTH) AF: 0.165 AC: 349 AN: 2112

Alfa AF: 0.177 Hom.: 317

Bravo AF: 0.154

Asia WGS AF: 0.177 AC: 614 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Congenital disorder of glycosylation (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs10699573; hg19: chr7-106842683;