rs7167392

Positions:

• chr15-42736394-G-A

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.477C>T​(p.Pro159=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 1,611,732 control chromosomes in the GnomAD database, including 45,844 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (5926 hom., cov: 32)
  • Exomes 𝑓: 0.23 (39918 hom.)
• Consequence: CDAN1 NM_138477.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.213

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=-0.79).
• BP6: Variant 15-42736394-G-A is Benign according to our data. Variant chr15-42736394-G-A is described in ClinVar as [Benign]. Clinvar id is 262378.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-42736394-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.213 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDAN1	NM_138477.4	c.477C>T	p.Pro159=	synonymous_variant	2/28	ENST00000356231.4	NP_612486.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDAN1	ENST00000356231.4	c.477C>T	p.Pro159=	synonymous_variant	2/28	1	NM_138477.4	ENSP00000348564	P1
CDAN1	ENST00000643434.1	c.91-313C>T		intron_variant, NMD_transcript_variant				ENSP00000494699

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39689 AN: 151870 Hom.: 5923 Cov.: 32

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.0947

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.0640

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.240

GnomAD3 exomes AF: 0.225 AC: 54525 AN: 242160 Hom.: 7229 AF XY: 0.234 AC XY: 30988 AN XY: 132578

Gnomad AFR exome AF: 0.403

Gnomad AMR exome AF: 0.113

Gnomad ASJ exome AF: 0.282

Gnomad EAS exome AF: 0.0639

Gnomad SAS exome AF: 0.366

Gnomad FIN exome AF: 0.247

Gnomad NFE exome AF: 0.214

Gnomad OTH exome AF: 0.221

GnomAD4 exome AF: 0.225 AC: 329005 AN: 1459744 Hom.: 39918 Cov.: 35 AF XY: 0.230 AC XY: 167136 AN XY: 726044

Gnomad4 AFR exome AF: 0.399

Gnomad4 AMR exome AF: 0.118

Gnomad4 ASJ exome AF: 0.280

Gnomad4 EAS exome AF: 0.0876

Gnomad4 SAS exome AF: 0.369

Gnomad4 FIN exome AF: 0.252

Gnomad4 NFE exome AF: 0.215

Gnomad4 OTH exome AF: 0.232

GnomAD4 genome AF: 0.261 AC: 39709 AN: 151988 Hom.: 5926 Cov.: 32 AF XY: 0.262 AC XY: 19462 AN XY: 74308

Gnomad4 AFR AF: 0.393

Gnomad4 AMR AF: 0.157

Gnomad4 ASJ AF: 0.283

Gnomad4 EAS AF: 0.0641

Gnomad4 SAS AF: 0.354

Gnomad4 FIN AF: 0.253

Gnomad4 NFE AF: 0.216

Gnomad4 OTH AF: 0.236

Alfa AF: 0.246 Hom.: 1452

Bravo AF: 0.257

Asia WGS AF: 0.206 AC: 715 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Congenital dyserythropoietic anemia, type I Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Nov 30, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	9.9
DANN	Benign	0.93

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: rs7167392; hg19: chr15-43028592; COSMIC: COSV51174689; COSMIC: COSV51174689;