18-74559420-C-T

Variant names:

• chr18-74559420-C-T
• rs200926840
• NM_032649.6:c.251C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_032649.6(CNDP1):​c.251C>T​(p.Thr84Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000195 in 1,612,960 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00058 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00015 (0 hom.)
• Consequence: CNDP1 NM_032649.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.417
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.013387561).
• BP6: Variant 18-74559420-C-T is Benign according to our data. Variant chr18-74559420-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3268080.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032649.6. 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
	CNDP1	NM_032649.6	MANE Select	c.251C>T	p.Thr84Met	missense	Exon 3 of 12	NP_116038.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNDP1	ENST00000358821.8	TSL:1 MANE Select	c.251C>T	p.Thr84Met	missense	Exon 3 of 12	ENSP00000351682.3	Q96KN2
	CNDP1	ENST00000864762.1		c.251C>T	p.Thr84Met	missense	Exon 3 of 12	ENSP00000534821.1
	CNDP1	ENST00000954332.1		c.251C>T	p.Thr84Met	missense	Exon 3 of 12	ENSP00000624391.1

Frequencies

GnomAD3 genomes AF: 0.000578 AC: 88 AN: 152140 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00491

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000252 AC: 63 AN: 250016 AF XY: 0.000288

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000782

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000290

Gnomad NFE exome AF: 0.000141

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000155 AC: 226 AN: 1460702 Hom.: 0 Cov.: 34 AF XY: 0.000169 AC XY: 123 AN XY: 726698

African (AFR) AF: 0.0000299 AC: 1 AN: 33474

American (AMR) AF: 0.000693 AC: 31 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.000359 AC: 31 AN: 86240

European-Finnish (FIN) AF: 0.000401 AC: 21 AN: 52370

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5752

European-Non Finnish (NFE) AF: 0.000119 AC: 132 AN: 1111942

Other (OTH) AF: 0.000132 AC: 8 AN: 60382

GnomAD4 genome AF: 0.000578 AC: 88 AN: 152258 Hom.: 2 Cov.: 32 AF XY: 0.000900 AC XY: 67 AN XY: 74446

African (AFR) AF: 0.0000481 AC: 2 AN: 41558

American (AMR) AF: 0.00491 AC: 75 AN: 15290

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10614

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

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.0000764 Hom.: 0

Bravo AF: 0.000408

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ExAC AF: 0.000165 AC: 20

EpiCase AF: 0.000218

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.097
DANN	Benign	0.96
DEOGEN2	Benign	0.013	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.013	T
MetaSVM	Benign	-0.95	T
PhyloP100		0.42
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.13
Sift	Benign	0.062	T
Sift4G	Benign	0.17	T
Vest4		0.11
MVP		0.10
MPC		0.16
ClinPred		0.040	T
GERP RS		-2.7
gMVP		0.29
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs200926840; hg19: chr18-72226655; COSMIC: COSV109434766; COSMIC: COSV109434766;