rs11151964

chr18-74534683-G-Achr18-74534683-G-T

Variant summary

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

The NM_032649.6(CNDP1):c.16G>A(p.Gly6Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,613,434 control chromosomes in the GnomAD database, including 11,681 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.13 (1306 hom., cov: 32)
  • Exomes 𝑓: 0.12 (10375 hom.)
• Consequence: CNDP1 NM_032649.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.123

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=0.0014539361).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNDP1	NM_032649.6	c.16G>A	p.Gly6Arg	missense_variant	1/12	ENST00000358821.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNDP1	ENST00000358821.8	c.16G>A	p.Gly6Arg	missense_variant	1/12	1	NM_032649.6	P1
CNDP1	ENST00000582365.1	c.16G>A	p.Gly6Arg	missense_variant	1/11	5
CNDP1	ENST00000585136.1	n.181G>A		non_coding_transcript_exon_variant	1/5	3

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19315 AN: 151980 Hom.: 1298 Cov.: 32

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.0950

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.0983

Gnomad SAS AF: 0.0868

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.134

GnomAD3 exomes AF: 0.112 AC: 28238 AN: 251258 Hom.: 1671 AF XY: 0.112 AC XY: 15275 AN XY: 135798

Gnomad AFR exome AF: 0.152

Gnomad AMR exome AF: 0.0710

Gnomad ASJ exome AF: 0.184

Gnomad EAS exome AF: 0.105

Gnomad SAS exome AF: 0.0856

Gnomad FIN exome AF: 0.116

Gnomad NFE exome AF: 0.120

Gnomad OTH exome AF: 0.126

GnomAD4 exome AF: 0.118 AC: 171985 AN: 1461336 Hom.: 10375 Cov.: 31 AF XY: 0.117 AC XY: 85206 AN XY: 726980

Gnomad4 AFR exome AF: 0.155

Gnomad4 AMR exome AF: 0.0743

Gnomad4 ASJ exome AF: 0.187

Gnomad4 EAS exome AF: 0.0868

Gnomad4 SAS exome AF: 0.0877

Gnomad4 FIN exome AF: 0.120

Gnomad4 NFE exome AF: 0.119

Gnomad4 OTH exome AF: 0.127

GnomAD4 genome AF: 0.127 AC: 19358 AN: 152098 Hom.: 1306 Cov.: 32 AF XY: 0.127 AC XY: 9445 AN XY: 74364

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.0948

Gnomad4 ASJ AF: 0.212

Gnomad4 EAS AF: 0.0984

Gnomad4 SAS AF: 0.0879

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.118

Gnomad4 OTH AF: 0.134

Alfa AF: 0.121 Hom.: 2875

Bravo AF: 0.127

TwinsUK AF: 0.126 AC: 469

ALSPAC AF: 0.120 AC: 463

ESP6500AA AF: 0.145 AC: 639

ESP6500EA AF: 0.121 AC: 1041

ExAC AF: 0.113 AC: 13679

Asia WGS AF: 0.0800 AC: 276 AN: 3478

EpiCase AF: 0.123

EpiControl AF: 0.127

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.78
Cadd	Benign	5.7
Dann	Benign	0.69
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.012	N
MetaRNN	Benign	0.0015	T;T
MetaSVM	Benign	-0.95	T
MutationTaster	Benign	1.0	P;P
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.19	N;.
REVEL	Benign	0.035
Sift	Uncertain	0.0090	D;.
Sift4G	Benign	0.071	T;D
Vest4		0.12
MutPred		0.13		Gain of MoRF binding (P = 0.0024);Gain of MoRF binding (P = 0.0024);
MPC		0.18
ClinPred		0.0075	T
GERP RS		-3.2
gMVP		0.25

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

Publications

LitVar

Other links and lift over

dbSNP: rs11151964; hg19: chr18-72201918;