rs62621182

chr18-74576973-G-Achr18-74576973-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032649.6(CNDP1):c.946G>A(p.Asp316Asn) variant causes a missense change. The variant allele was found at a frequency of 0.022 in 1,613,270 control chromosomes in the GnomAD database, including 1,361 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.048 (349 hom., cov: 32)
  • Exomes 𝑓: 0.019 (1012 hom.)
• Consequence: CNDP1 NM_032649.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.78

Genes affected

CNDP1 (HGNC:20675): (carnosine dipeptidase 1) This gene encodes a member of the M20 metalloprotease family. The encoded protein is specifically expressed in the brain, is a homodimeric dipeptidase which was identified as human carnosinase. This gene contains trinucleotide (CTG) repeat length polymorphism in the coding region. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017642379).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNDP1	NM_032649.6	c.946G>A	p.Asp316Asn	missense_variant	8/12	ENST00000358821.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNDP1	ENST00000358821.8	c.946G>A	p.Asp316Asn	missense_variant	8/12	1	NM_032649.6	P1
CNDP1	ENST00000582365.1	c.817G>A	p.Asp273Asn	missense_variant	7/11	5
CNDP1	ENST00000582461.1	n.694G>A		non_coding_transcript_exon_variant	1/3	5
CNDP1	ENST00000584004.5	n.470G>A		non_coding_transcript_exon_variant	3/7	2

Frequencies

GnomAD3 genomes AF: 0.0476 AC: 7246 AN: 152088 Hom.: 349 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0470

Gnomad ASJ AF: 0.0458

Gnomad EAS AF: 0.0368

Gnomad SAS AF: 0.0955

Gnomad FIN AF: 0.00538

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00872

Gnomad OTH AF: 0.0435

GnomAD3 exomes AF: 0.0347 AC: 8688 AN: 250732 Hom.: 418 AF XY: 0.0367 AC XY: 4976 AN XY: 135522

Gnomad AFR exome AF: 0.120

Gnomad AMR exome AF: 0.0282

Gnomad ASJ exome AF: 0.0472

Gnomad EAS exome AF: 0.0311

Gnomad SAS exome AF: 0.108

Gnomad FIN exome AF: 0.00675

Gnomad NFE exome AF: 0.00994

Gnomad OTH exome AF: 0.0303

GnomAD4 exome AF: 0.0193 AC: 28226 AN: 1461064 Hom.: 1012 Cov.: 31 AF XY: 0.0220 AC XY: 15964 AN XY: 726756

Gnomad4 AFR exome AF: 0.116

Gnomad4 AMR exome AF: 0.0308

Gnomad4 ASJ exome AF: 0.0479

Gnomad4 EAS exome AF: 0.0348

Gnomad4 SAS exome AF: 0.106

Gnomad4 FIN exome AF: 0.00702

Gnomad4 NFE exome AF: 0.00796

Gnomad4 OTH exome AF: 0.0287

GnomAD4 genome AF: 0.0477 AC: 7257 AN: 152206 Hom.: 349 Cov.: 32 AF XY: 0.0495 AC XY: 3686 AN XY: 74420

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.0468

Gnomad4 ASJ AF: 0.0458

Gnomad4 EAS AF: 0.0367

Gnomad4 SAS AF: 0.0958

Gnomad4 FIN AF: 0.00538

Gnomad4 NFE AF: 0.00872

Gnomad4 OTH AF: 0.0431

Alfa AF: 0.0160 Hom.: 90

Bravo AF: 0.0507

TwinsUK AF: 0.00620 AC: 23

ALSPAC AF: 0.00701 AC: 27

ESP6500AA AF: 0.113 AC: 498

ESP6500EA AF: 0.0106 AC: 91

ExAC AF: 0.0367 AC: 4451

Asia WGS AF: 0.0640 AC: 221 AN: 3478

EpiCase AF: 0.0110

EpiControl AF: 0.0115

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.69
Cadd	Benign	20
Dann	Uncertain	1.0
Eigen	Benign	-0.039
Eigen_PC	Benign	0.061
FATHMM_MKL	Uncertain	0.82	D
MetaRNN	Benign	0.0018	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-3.4	D;.
REVEL	Benign	0.11
Sift	Benign	0.055	T;.
Sift4G	Benign	0.11	T;T
Vest4		0.10
MPC		0.15
ClinPred		0.018	T
GERP RS		4.2
gMVP		0.72

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: rs62621182; hg19: chr18-72244208; COSMIC: COSV62593911; COSMIC: COSV62593911;