rs12327522

Variant names:

• chr18-74569184-A-T
• rs12327522
• NM_032649.6:c.756+1751A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032649.6(CNDP1):​c.756+1751A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 152,004 control chromosomes in the GnomAD database, including 7,012 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 0.30 (7012 hom., cov: 31)
• Consequence: CNDP1 NM_032649.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.139
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNDP1	NM_032649.6	c.756+1751A>T		intron_variant	Intron 6 of 11	ENST00000358821.8	NP_116038.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNDP1	ENST00000358821.8	c.756+1751A>T		intron_variant	Intron 6 of 11	1	NM_032649.6	ENSP00000351682.3
CNDP1	ENST00000582365.1	c.627+1751A>T		intron_variant	Intron 5 of 10	5		ENSP00000462096.1
CNDP1	ENST00000584004.5	n.280+1751A>T		intron_variant	Intron 1 of 6	2
CNDP1	ENST00000584316.5	n.*224+1751A>T		intron_variant	Intron 3 of 4	4		ENSP00000463807.1

Frequencies

GnomAD3 genomes AF: 0.296 AC: 44982 AN: 151886 Hom.: 7008 Cov.: 31

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.310

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.296 AC: 45013 AN: 152004 Hom.: 7012 Cov.: 31 AF XY: 0.300 AC XY: 22256 AN XY: 74290

African (AFR) AF: 0.214 AC: 8877 AN: 41442

American (AMR) AF: 0.388 AC: 5925 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 891 AN: 3470

East Asian (EAS) AF: 0.438 AC: 2252 AN: 5146

South Asian (SAS) AF: 0.279 AC: 1343 AN: 4814

European-Finnish (FIN) AF: 0.347 AC: 3662 AN: 10568

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.310 AC: 21097 AN: 67970

Other (OTH) AF: 0.312 AC: 659 AN: 2114

Alfa AF: 0.299 Hom.: 954

Bravo AF: 0.299

Asia WGS AF: 0.377 AC: 1310 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.8
DANN	Benign	0.75
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

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: rs12327522; hg19: chr18-72236419;