18-74571177-ACT-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_032649.6(CNDP1):c.757-6_757-5del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00265 in 1,586,890 control chromosomes in the GnomAD database, including 133 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0039 (12 hom., cov: 32)
  • Exomes 𝑓: 0.0025 (121 hom.)
• Consequence: CNDP1 NM_032649.6 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.806

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 -10 ACMG points.

• BP6: Variant 18-74571177-ACT-A is Benign according to our data. Variant chr18-74571177-ACT-A is described in ClinVar as [Benign]. Clinvar id is 770278.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.067 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNDP1	NM_032649.6	c.757-6_757-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000358821.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNDP1	ENST00000358821.8	c.757-6_757-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_032649.6	P1
CNDP1	ENST00000582365.1	c.628-6_628-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5
CNDP1	ENST00000584316.5	c.*225-6_*225-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		4
CNDP1	ENST00000584004.5	n.281-6_281-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00389 AC: 592 AN: 152066 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.00126

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0330

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.0114 AC: 2850 AN: 251080 Hom.: 109 AF XY: 0.00871 AC XY: 1182 AN XY: 135692

Gnomad AFR exome AF: 0.000862

Gnomad AMR exome AF: 0.0775

Gnomad ASJ exome AF: 0.000397

Gnomad EAS exome AF: 0.00163

Gnomad SAS exome AF: 0.00183

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000150

Gnomad OTH exome AF: 0.00866

GnomAD4 exome AF: 0.00252 AC: 3614 AN: 1434706 Hom.: 121 AF XY: 0.00221 AC XY: 1579 AN XY: 715472

Gnomad4 AFR exome AF: 0.000547

Gnomad4 AMR exome AF: 0.0691

Gnomad4 ASJ exome AF: 0.000462

Gnomad4 EAS exome AF: 0.00232

Gnomad4 SAS exome AF: 0.00186

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000130

Gnomad4 OTH exome AF: 0.00177

GnomAD4 genome AF: 0.00389 AC: 592 AN: 152184 Hom.: 12 Cov.: 32 AF XY: 0.00426 AC XY: 317 AN XY: 74408

Gnomad4 AFR AF: 0.00125

Gnomad4 AMR AF: 0.0329

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.00187

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00282 Hom.: 1

Bravo AF: 0.00682

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.28		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.28		Position offset: 9

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

Publications

LitVar

Other links and lift over

dbSNP: rs201503578; hg19: chr18-72238412;