15-42724349-T-C

Variant names:

• chr15-42724349-T-C
• rs3742987
• NM_138477.4:c.*142A>G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_138477.4(CDAN1):​c.*142A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 1,134,980 control chromosomes in the GnomAD database, including 58,741 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (18329 hom., cov: 33)
  • Exomes 𝑓: 0.26 (40412 hom.)
• Consequence: CDAN1 NM_138477.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.950

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]

ENSG00000278769 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 15-42724349-T-C is Benign according to our data. Variant chr15-42724349-T-C is described in ClinVar as [Benign]. Clinvar id is 315916.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.833 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDAN1	NM_138477.4	c.*142A>G		3_prime_UTR_variant	Exon 28 of 28	ENST00000356231.4	NP_612486.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDAN1	ENST00000356231	c.*142A>G		3_prime_UTR_variant	Exon 28 of 28	1	NM_138477.4	ENSP00000348564.3

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61617 AN: 152104 Hom.: 18269 Cov.: 33

Gnomad AFR AF: 0.840

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.356

GnomAD4 exome AF: 0.261 AC: 256406 AN: 982758 Hom.: 40412 Cov.: 12 AF XY: 0.267 AC XY: 132123 AN XY: 495586

Gnomad4 AFR exome AF: 0.860

Gnomad4 AMR exome AF: 0.161

Gnomad4 ASJ exome AF: 0.318

Gnomad4 EAS exome AF: 0.246

Gnomad4 SAS exome AF: 0.439

Gnomad4 FIN exome AF: 0.254

Gnomad4 NFE exome AF: 0.225

Gnomad4 OTH exome AF: 0.296

GnomAD4 genome AF: 0.406 AC: 61731 AN: 152222 Hom.: 18329 Cov.: 33 AF XY: 0.402 AC XY: 29910 AN XY: 74426

Gnomad4 AFR AF: 0.840

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.320

Gnomad4 EAS AF: 0.250

Gnomad4 SAS AF: 0.427

Gnomad4 FIN AF: 0.254

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.351

Alfa AF: 0.239 Hom.: 5151

Bravo AF: 0.418

Asia WGS AF: 0.360 AC: 1251 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 10, 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

- -

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.0
DANN	Benign	0.33

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: rs3742987; hg19: chr15-43016547; COSMIC: COSV51915842; COSMIC: COSV51915842;