chr15-42736313-G-C

Variant names:

• chr15-42736313-G-C
• rs12594325
• NM_138477.4:c.558C>G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_138477.4(CDAN1):​c.558C>G​(p.Pro186Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0166 in 1,612,410 control chromosomes in the GnomAD database, including 1,423 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.057 (618 hom., cov: 32)
  • Exomes 𝑓: 0.012 (805 hom.)
• Consequence: CDAN1 NM_138477.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.0420

Genes affected

CDAN1 (HGNC:1713): (codanin 1) This gene encodes a protein that appears to play a role in nuclear envelope integrity, possibly related to microtubule attachments. Mutations in this gene cause congenital dyserythropoietic anemia type I, a disease resulting in morphological and functional abnormalities of erythropoiesis. [provided by RefSeq, Jul 2009]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 15-42736313-G-C is Benign according to our data. Variant chr15-42736313-G-C is described in ClinVar as [Benign]. Clinvar id is 262379.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.042 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDAN1	NM_138477.4	c.558C>G	p.Pro186Pro	synonymous_variant	Exon 2 of 28	ENST00000356231.4	NP_612486.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDAN1	ENST00000356231.4	c.558C>G	p.Pro186Pro	synonymous_variant	Exon 2 of 28	1	NM_138477.4	ENSP00000348564.3
CDAN1	ENST00000643434.1	n.91-232C>G		intron_variant	Intron 1 of 24			ENSP00000494699.1
CDAN1	ENST00000563260.1	c.*249C>G		downstream_gene_variant		3		ENSP00000455536.1

Frequencies

GnomAD3 genomes AF: 0.0565 AC: 8593 AN: 152026 Hom.: 616 Cov.: 32

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0217

Gnomad ASJ AF: 0.0297

Gnomad EAS AF: 0.0582

Gnomad SAS AF: 0.0265

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00507

Gnomad OTH AF: 0.0411

GnomAD3 exomes AF: 0.0246 AC: 6059 AN: 246502 Hom.: 327 AF XY: 0.0225 AC XY: 3025 AN XY: 134220

Gnomad AFR exome AF: 0.178

Gnomad AMR exome AF: 0.00952

Gnomad ASJ exome AF: 0.0293

Gnomad EAS exome AF: 0.0649

Gnomad SAS exome AF: 0.0280

Gnomad FIN exome AF: 0.000378

Gnomad NFE exome AF: 0.00500

Gnomad OTH exome AF: 0.0176

GnomAD4 exome AF: 0.0125 AC: 18224 AN: 1460268 Hom.: 805 Cov.: 32 AF XY: 0.0126 AC XY: 9119 AN XY: 726446

Gnomad4 AFR exome AF: 0.188

Gnomad4 AMR exome AF: 0.0113

Gnomad4 ASJ exome AF: 0.0324

Gnomad4 EAS exome AF: 0.0512

Gnomad4 SAS exome AF: 0.0288

Gnomad4 FIN exome AF: 0.000340

Gnomad4 NFE exome AF: 0.00420

Gnomad4 OTH exome AF: 0.0212

GnomAD4 genome AF: 0.0566 AC: 8613 AN: 152142 Hom.: 618 Cov.: 32 AF XY: 0.0547 AC XY: 4068 AN XY: 74384

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.0217

Gnomad4 ASJ AF: 0.0297

Gnomad4 EAS AF: 0.0582

Gnomad4 SAS AF: 0.0268

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.00506

Gnomad4 OTH AF: 0.0411

Alfa AF: 0.0106 Hom.: 13

Bravo AF: 0.0632

Asia WGS AF: 0.0480 AC: 167 AN: 3478

EpiCase AF: 0.00611

EpiControl AF: 0.00516

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Congenital dyserythropoietic anemia, type I Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Anemia, congenital dyserythropoietic, type 1a Benign:1

Nov 08, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	5.5
DANN	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs12594325; hg19: chr15-43028511; COSMIC: COSV51177740; COSMIC: COSV51177740;