chr15-42726361-C-T

Position:

• chr15-42726361-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_138477.4(CDAN1):​c.3153G>A​(p.Glu1051=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0221 in 1,598,168 control chromosomes in the GnomAD database, including 1,583 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.061 (649 hom., cov: 33)
  • Exomes 𝑓: 0.018 (934 hom.)
• Consequence: CDAN1 NM_138477.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.470

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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 15-42726361-C-T is Benign according to our data. Variant chr15-42726361-C-T is described in ClinVar as [Benign]. Clinvar id is 262374.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.47 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDAN1	NM_138477.4	c.3153G>A	p.Glu1051=	synonymous_variant	24/28	ENST00000356231.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDAN1	ENST00000356231.4	c.3153G>A	p.Glu1051=	synonymous_variant	24/28	1	NM_138477.4	P1
CDAN1	ENST00000562465.5	c.*55G>A		3_prime_UTR_variant, NMD_transcript_variant	11/15	1
CDAN1	ENST00000643434.1	c.*2284G>A		3_prime_UTR_variant, NMD_transcript_variant	22/25

Frequencies

GnomAD3 genomes AF: 0.0613 AC: 9337 AN: 152216 Hom.: 647 Cov.: 33

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0243

Gnomad ASJ AF: 0.0351

Gnomad EAS AF: 0.0586

Gnomad SAS AF: 0.0457

Gnomad FIN AF: 0.00386

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0107

Gnomad OTH AF: 0.0454

GnomAD3 exomes AF: 0.0302 AC: 6660 AN: 220590 Hom.: 312 AF XY: 0.0292 AC XY: 3480 AN XY: 119296

Gnomad AFR exome AF: 0.179

Gnomad AMR exome AF: 0.0125

Gnomad ASJ exome AF: 0.0363

Gnomad EAS exome AF: 0.0654

Gnomad SAS exome AF: 0.0456

Gnomad FIN exome AF: 0.00335

Gnomad NFE exome AF: 0.0105

Gnomad OTH exome AF: 0.0223

GnomAD4 exome AF: 0.0179 AC: 25941 AN: 1445834 Hom.: 934 Cov.: 33 AF XY: 0.0185 AC XY: 13266 AN XY: 717826

Gnomad4 AFR exome AF: 0.191

Gnomad4 AMR exome AF: 0.0149

Gnomad4 ASJ exome AF: 0.0385

Gnomad4 EAS exome AF: 0.0509

Gnomad4 SAS exome AF: 0.0473

Gnomad4 FIN exome AF: 0.00359

Gnomad4 NFE exome AF: 0.00919

Gnomad4 OTH exome AF: 0.0268

GnomAD4 genome AF: 0.0614 AC: 9358 AN: 152334 Hom.: 649 Cov.: 33 AF XY: 0.0598 AC XY: 4455 AN XY: 74498

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.0242

Gnomad4 ASJ AF: 0.0351

Gnomad4 EAS AF: 0.0587

Gnomad4 SAS AF: 0.0460

Gnomad4 FIN AF: 0.00386

Gnomad4 NFE AF: 0.0107

Gnomad4 OTH AF: 0.0449

Alfa AF: 0.0243 Hom.: 57

Bravo AF: 0.0673

Asia WGS AF: 0.0540 AC: 190 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	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
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 22, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	5.2
DANN	Benign	0.48

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: rs28661826; hg19: chr15-43018559;