8-96784889-G-GA

Variant names:

• chr8-96784889-G-GA
• NM_016134.4:c.1dupA

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_016134.4(CPQ):​c.1dupA​(p.Met1fs) variant causes a frameshift, start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000512 in 1,566,230 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0023 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00032 (1 hom.)
• Consequence: CPQ NM_016134.4 frameshift, start_lost
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.56

Genes affected

CPQ (HGNC:16910): (carboxypeptidase Q) This gene encodes a metallopeptidase that belongs to the peptidase M28 family. The encoded protein may catalyze the cleavage of dipeptides with unsubstituted terminals into amino acids. [provided by RefSeq, Jul 2013]

LOC124901985 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 8-96784889-G-GA is Benign according to our data. Variant chr8-96784889-G-GA is described in ClinVar as [Likely_benign]. Clinvar id is 422436.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPQ	NM_016134.4	c.1dupA	p.Met1fs	frameshift_variant, start_lost	Exon 2 of 8	ENST00000220763.10	NP_057218.1
LOC124901985	XR_007061019.1	n.354+6652dupT		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPQ	ENST00000220763.10	c.1dupA	p.Met1fs	frameshift_variant, start_lost	Exon 2 of 8	1	NM_016134.4	ENSP00000220763.5

Frequencies

GnomAD3 genomes AF: 0.00233 AC: 348 AN: 149246 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00820

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000335

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000100

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000119

Gnomad OTH AF: 0.000488

GnomAD4 exome AF: 0.000320 AC: 454 AN: 1416876 Hom.: 1 Cov.: 31 AF XY: 0.000274 AC XY: 193 AN XY: 704154

Gnomad4 AFR exome AF: 0.00817

Gnomad4 AMR exome AF: 0.000613

Gnomad4 ASJ exome AF: 0.000207

Gnomad4 EAS exome AF: 0.0000768

Gnomad4 SAS exome AF: 0.000294

Gnomad4 FIN exome AF: 0.000115

Gnomad4 NFE exome AF: 0.000104

Gnomad4 OTH exome AF: 0.000446

GnomAD4 genome AF: 0.00233 AC: 348 AN: 149354 Hom.: 3 Cov.: 32 AF XY: 0.00232 AC XY: 169 AN XY: 72812

Gnomad4 AFR AF: 0.00817

Gnomad4 AMR AF: 0.000334

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000100

Gnomad4 NFE AF: 0.000119

Gnomad4 OTH AF: 0.000483

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Oct 27, 2016

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-97797117;