7-107202238-A-ATCTT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_006348.5(COG5):c.*1277_*1278insAAGA 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

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

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COG5	NM_006348.5	c.*1277_*1278insAAGA		3_prime_UTR_variant	22/22	ENST00000297135.9
HBP1	NM_012257.4	c.*809_*812dup		3_prime_UTR_variant	11/11	ENST00000222574.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HBP1	ENST00000222574.9	c.*809_*812dup		3_prime_UTR_variant	11/11	1	NM_012257.4	P1
COG5	ENST00000297135.9	c.*1277_*1278insAAGA		3_prime_UTR_variant	22/22	1	NM_006348.5	P2
COG5	ENST00000347053.8	c.*1277_*1278insAAGA		3_prime_UTR_variant	21/21	1		A2
HBP1	ENST00000468410.5	c.*809_*812dup		3_prime_UTR_variant	11/11	2		P1

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

Gnomad4 FIN exome AF: 0.168

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Gnomad4 AFR AF: 0.0432

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.225

Gnomad4 EAS AF: 0.140

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.169

Gnomad4 NFE AF: 0.216

Gnomad4 OTH AF: 0.165

Alfa AF: 0.177 Hom.: 317

Bravo AF: 0.154

Asia WGS AF: 0.177 AC: 614 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Congenital disorder of glycosylation Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10699573; hg19: chr7-106842683;