rs149981793

Variant names:

• chr8-96785171-T-G
• rs149981793
• NM_016134.4:c.274T>G

Your query was ambiguous. Multiple possible variants found:

• chr8-96785171-T-G
• chr8-96785171-T-C

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_016134.4(CPQ):​c.274T>G​(p.Tyr92Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000684 in 1,613,614 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0035 (6 hom., cov: 32)
  • Exomes 𝑓: 0.00039 (4 hom.)
• Consequence: CPQ NM_016134.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.49
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0075683296).
• BP6: Variant 8-96785171-T-G is Benign according to our data. Variant chr8-96785171-T-G is described in ClinVar as Benign. ClinVar VariationId is 785878.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016134.4. 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
	CPQ	NM_016134.4	MANE Select	c.274T>G	p.Tyr92Asp	missense	Exon 2 of 8	NP_057218.1	Q9Y646

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPQ	ENST00000220763.10	TSL:1 MANE Select	c.274T>G	p.Tyr92Asp	missense	Exon 2 of 8	ENSP00000220763.5	Q9Y646
	CPQ	ENST00000960277.1		c.274T>G	p.Tyr92Asp	missense	Exon 2 of 9	ENSP00000630336.1
	CPQ	ENST00000863818.1		c.274T>G	p.Tyr92Asp	missense	Exon 2 of 9	ENSP00000533877.1

Frequencies

GnomAD3 genomes AF: 0.00353 AC: 537 AN: 152060 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0122

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.000955 AC: 239 AN: 250298 AF XY: 0.000717

Gnomad AFR exome AF: 0.0129

Gnomad AMR exome AF: 0.000696

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000354

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000387 AC: 566 AN: 1461436 Hom.: 4 Cov.: 31 AF XY: 0.000334 AC XY: 243 AN XY: 727016

African (AFR) AF: 0.0131 AC: 437 AN: 33462

American (AMR) AF: 0.000694 AC: 31 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39602

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86248

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53398

Middle Eastern (MID) AF: 0.000868 AC: 5 AN: 5760

European-Non Finnish (NFE) AF: 0.0000360 AC: 40 AN: 1111794

Other (OTH) AF: 0.000778 AC: 47 AN: 60376

GnomAD4 genome AF: 0.00353 AC: 537 AN: 152178 Hom.: 6 Cov.: 32 AF XY: 0.00343 AC XY: 255 AN XY: 74396

African (AFR) AF: 0.0122 AC: 506 AN: 41530

American (AMR) AF: 0.00144 AC: 22 AN: 15284

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67982

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00137 Hom.: 2

Bravo AF: 0.00429

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0120 AC: 53

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00114 AC: 138

Asia WGS AF: 0.00115 AC: 4 AN: 3476

EpiCase AF: 0.0000546

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: 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
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	18
DANN	Benign	0.81
DEOGEN2	Benign	0.056	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.43
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.55	T
MetaRNN	Benign	0.0076	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		2.5
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.16
Sift	Benign	0.094	T
Sift4G	Benign	0.11	T
Polyphen		0.023	B
Vest4		0.54
MVP		0.37
MPC		0.23
ClinPred		0.069	T
GERP RS		2.0
Varity_R		0.19
gMVP		0.87
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs149981793; hg19: chr8-97797399;