rs76599133

Variant names:

• chr15-42735637-G-T
• rs76599133
• NM_138477.4:c.816C>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.816C>A​(p.Thr272Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0175 in 1,614,048 control chromosomes in the GnomAD database, including 1,784 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.060 (776 hom., cov: 32)
  • Exomes 𝑓: 0.013 (1008 hom.)
• Consequence: CDAN1 NM_138477.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.228

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=-0.63).
• BP6: Variant 15-42735637-G-T is Benign according to our data. Variant chr15-42735637-G-T is described in ClinVar as [Benign]. Clinvar id is 262380.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.228 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDAN1	NM_138477.4	c.816C>A	p.Thr272Thr	synonymous_variant	Exon 4 of 28	ENST00000356231.4	NP_612486.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDAN1	ENST00000356231.4	c.816C>A	p.Thr272Thr	synonymous_variant	Exon 4 of 28	1	NM_138477.4	ENSP00000348564.3
CDAN1	ENST00000643434.1	n.*115C>A		non_coding_transcript_exon_variant	Exon 3 of 25			ENSP00000494699.1
CDAN1	ENST00000643434.1	n.*115C>A		3_prime_UTR_variant	Exon 3 of 25			ENSP00000494699.1

Frequencies

GnomAD3 genomes AF: 0.0601 AC: 9137 AN: 152092 Hom.: 769 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0253

Gnomad ASJ AF: 0.00518

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.0365

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00315

Gnomad OTH AF: 0.0465

GnomAD3 exomes AF: 0.0299 AC: 7491 AN: 250348 Hom.: 484 AF XY: 0.0271 AC XY: 3679 AN XY: 135738

Gnomad AFR exome AF: 0.189

Gnomad AMR exome AF: 0.0145

Gnomad ASJ exome AF: 0.00578

Gnomad EAS exome AF: 0.128

Gnomad SAS exome AF: 0.0354

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.00343

Gnomad OTH exome AF: 0.0157

GnomAD4 exome AF: 0.0131 AC: 19091 AN: 1461840 Hom.: 1008 Cov.: 32 AF XY: 0.0131 AC XY: 9529 AN XY: 727234

Gnomad4 AFR exome AF: 0.191

Gnomad4 AMR exome AF: 0.0165

Gnomad4 ASJ exome AF: 0.00520

Gnomad4 EAS exome AF: 0.104

Gnomad4 SAS exome AF: 0.0345

Gnomad4 FIN exome AF: 0.000300

Gnomad4 NFE exome AF: 0.00270

Gnomad4 OTH exome AF: 0.0258

GnomAD4 genome AF: 0.0603 AC: 9172 AN: 152208 Hom.: 776 Cov.: 32 AF XY: 0.0588 AC XY: 4375 AN XY: 74432

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.0253

Gnomad4 ASJ AF: 0.00518

Gnomad4 EAS AF: 0.122

Gnomad4 SAS AF: 0.0365

Gnomad4 FIN AF: 0.000659

Gnomad4 NFE AF: 0.00315

Gnomad4 OTH AF: 0.0456

Alfa AF: 0.0331 Hom.: 134

Bravo AF: 0.0670

Asia WGS AF: 0.0810 AC: 282 AN: 3478

EpiCase AF: 0.00463

EpiControl AF: 0.00409

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 04, 2021

GeneDx

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 15, 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	-0.63
CADD	Benign	6.0
DANN	Benign	0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs76599133; hg19: chr15-43027835; COSMIC: COSV51177738; COSMIC: COSV51177738;