ENST00000567047.2:n.192+78C>A

Variant names:

• chr16-19067503-G-T
• rs116281108
• ENST00000567047.2:n.192+78C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000567047.2(COQ7-DT):​n.192+78C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00284 in 713,496 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0097 (33 hom., cov: 33)
  • Exomes 𝑓: 0.00098 (13 hom.)
• Consequence: COQ7-DT ENST00000567047.2 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.75
• Publications: 0 publications found

Genes affected

COQ7-DT (HGNC:55362): (COQ7 divergent transcript)

COQ7 (HGNC:2244): (coenzyme Q7, hydroxylase) The protein encoded by this gene is similar to a mitochondrial di-iron containing hydroxylase in Saccharomyces cerevisiae that is involved with ubiquinone biosynthesis. Mutations in the yeast gene lead to slower development and longer life span. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2010]

COQ7 Gene-Disease associations (from GenCC):

• primary coenzyme Q10 deficiency 8

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 16-19067503-G-T is Benign according to our data. Variant chr16-19067503-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1316734.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00969 (1476/152250) while in subpopulation AFR AF = 0.0335 (1390/41544). AF 95% confidence interval is 0.032. There are 33 homozygotes in GnomAd4. There are 686 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 33 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000567047.2. 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
	COQ7-DT	NR_119379.1		n.111+78C>A		intron	N/A
	COQ7-DT	NR_119380.1		n.141+48C>A		intron	N/A
	COQ7-DT	NR_119381.1		n.111+78C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COQ7-DT	ENST00000567047.2	TSL:2	n.192+78C>A		intron	N/A
	COQ7-DT	ENST00000568971.5	TSL:2	n.91+48C>A		intron	N/A
	COQ7-DT	ENST00000571934.5	TSL:5	n.91+48C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00971 AC: 1477 AN: 152132 Hom.: 33 Cov.: 33

Gnomad AFR AF: 0.0336

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00491

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00239

GnomAD4 exome AF: 0.000980 AC: 550 AN: 561246 Hom.: 13 Cov.: 7 AF XY: 0.000851 AC XY: 254 AN XY: 298626

African (AFR) AF: 0.0323 AC: 423 AN: 13084

American (AMR) AF: 0.00271 AC: 57 AN: 21046

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15046

East Asian (EAS) AF: 0.00 AC: 0 AN: 31122

South Asian (SAS) AF: 0.0000182 AC: 1 AN: 54826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38796

Middle Eastern (MID) AF: 0.000800 AC: 3 AN: 3750

European-Non Finnish (NFE) AF: 0.0000311 AC: 11 AN: 354146

Other (OTH) AF: 0.00187 AC: 55 AN: 29430

GnomAD4 genome AF: 0.00969 AC: 1476 AN: 152250 Hom.: 33 Cov.: 33 AF XY: 0.00921 AC XY: 686 AN XY: 74456

African (AFR) AF: 0.0335 AC: 1390 AN: 41544

American (AMR) AF: 0.00491 AC: 75 AN: 15288

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68020

Other (OTH) AF: 0.00237 AC: 5 AN: 2112

Alfa AF: 0.00378 Hom.: 1

Bravo AF: 0.0106

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.065
DANN	Benign	0.70
PhyloP100		-1.8
PromoterAI		-0.10	Neutral

Splicing

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

Other links and lift over

dbSNP: rs116281108; hg19: chr16-19078825;