18-74583526-T-C

Variant names:

• chr18-74583526-T-C
• rs11659237
• NM_032649.6:c.1310-35T>C

Variant summary

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

The NM_032649.6(CNDP1):​c.1310-35T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 1,601,126 control chromosomes in the GnomAD database, including 353,701 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.61 (29038 hom., cov: 31)
  • Exomes 𝑓: 0.67 (324663 hom.)
• Consequence: CNDP1 NM_032649.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.40
• Publications: 11 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]

ZNF407-AS1 (HGNC:44331): (ZNF407 antisense RNA 1)

LOC124904324 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 2 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNDP1	NM_032649.6	c.1310-35T>C		intron_variant	Intron 10 of 11	ENST00000358821.8	NP_116038.4
LOC124904324	XR_007066415.1	n.152A>G		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNDP1	ENST00000358821.8	c.1310-35T>C		intron_variant	Intron 10 of 11	1	NM_032649.6	ENSP00000351682.3

Frequencies

GnomAD3 genomes AF: 0.609 AC: 92431 AN: 151852 Hom.: 29033 Cov.: 31

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.647

Gnomad AMR AF: 0.688

Gnomad ASJ AF: 0.665

Gnomad EAS AF: 0.646

Gnomad SAS AF: 0.727

Gnomad FIN AF: 0.676

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.666

Gnomad OTH AF: 0.643

GnomAD2 exomes AF: 0.669 AC: 167278 AN: 250178 AF XY: 0.674

Gnomad AFR exome AF: 0.437

Gnomad AMR exome AF: 0.723

Gnomad ASJ exome AF: 0.647

Gnomad EAS exome AF: 0.653

Gnomad FIN exome AF: 0.687

Gnomad NFE exome AF: 0.669

Gnomad OTH exome AF: 0.689

GnomAD4 exome AF: 0.667 AC: 966994 AN: 1449156 Hom.: 324663 Cov.: 27 AF XY: 0.670 AC XY: 482722 AN XY: 720992

African (AFR) AF: 0.432 AC: 14361 AN: 33242

American (AMR) AF: 0.720 AC: 32123 AN: 44640

Ashkenazi Jewish (ASJ) AF: 0.648 AC: 16805 AN: 25930

East Asian (EAS) AF: 0.654 AC: 25845 AN: 39548

South Asian (SAS) AF: 0.726 AC: 62337 AN: 85880

European-Finnish (FIN) AF: 0.683 AC: 36398 AN: 53314

Middle Eastern (MID) AF: 0.714 AC: 4100 AN: 5742

European-Non Finnish (NFE) AF: 0.668 AC: 735539 AN: 1100902

Other (OTH) AF: 0.659 AC: 39486 AN: 59958

GnomAD4 genome AF: 0.608 AC: 92470 AN: 151970 Hom.: 29038 Cov.: 31 AF XY: 0.612 AC XY: 45446 AN XY: 74272

African (AFR) AF: 0.441 AC: 18269 AN: 41432

American (AMR) AF: 0.689 AC: 10530 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.665 AC: 2305 AN: 3468

East Asian (EAS) AF: 0.647 AC: 3334 AN: 5154

South Asian (SAS) AF: 0.726 AC: 3500 AN: 4818

European-Finnish (FIN) AF: 0.676 AC: 7131 AN: 10544

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.666 AC: 45255 AN: 67944

Other (OTH) AF: 0.640 AC: 1352 AN: 2114

Alfa AF: 0.633 Hom.: 6361

Bravo AF: 0.605

Asia WGS AF: 0.663 AC: 2308 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.6
DANN	Benign	0.45
PhyloP100		1.4
BranchPoint Hunter		2.0
Mutation Taster		=12/88	disease causing

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

Other links and lift over

dbSNP: rs11659237; hg19: chr18-72250762; COSMIC: COSV62594146;