rs760132974

Variant names:

• chr19-40692176-G-A
• rs760132974
• NM_024876.4:c.1494C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-40692176-G-A
• chr19-40692176-G-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_024876.4(COQ8B):​c.1494C>T​(p.Ala498Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,443,732 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A498A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: COQ8B NM_024876.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.94

Genes affected

COQ8B (HGNC:19041): (coenzyme Q8B) This gene encodes a protein with two copies of a domain found in protein kinases. The encoded protein has a complete protein kinase catalytic domain, and a truncated domain that contains only the active and binding sites of the protein kinase domain, however, it is not known whether the protein has any kinase activity. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP7: Synonymous conserved (PhyloP=2.94 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COQ8B	NM_024876.4	c.1494C>T	p.Ala498Ala	synonymous_variant	Exon 15 of 15	ENST00000324464.8	NP_079152.3
COQ8B	NM_001142555.3	c.1371C>T	p.Ala457Ala	synonymous_variant	Exon 14 of 14		NP_001136027.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COQ8B	ENST00000324464.8	c.1494C>T	p.Ala498Ala	synonymous_variant	Exon 15 of 15	1	NM_024876.4	ENSP00000315118.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000469 AC: 1 AN: 213146 Hom.: 0 AF XY: 0.00000865 AC XY: 1 AN XY: 115550

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000363

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1443732 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 716872

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000168

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	9.0
DANN	Benign	0.81

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

Publications

LitVar

Other links and lift over

dbSNP: rs760132974; hg19: chr19-41198081;