rs75993383

chr15-42730578-C-T

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.2174+20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00473 in 1,613,924 control chromosomes in the GnomAD database, including 197 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (105 hom., cov: 33)
  • Exomes 𝑓: 0.0030 (92 hom.)
• Consequence: CDAN1 NM_138477.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.299

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 15-42730578-C-T is Benign according to our data. Variant chr15-42730578-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 262369.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.069 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDAN1	NM_138477.4	c.2174+20G>A		intron_variant		ENST00000356231.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDAN1	ENST00000356231.4	c.2174+20G>A		intron_variant		1	NM_138477.4	P1
CDAN1	ENST00000562465.5	c.167+20G>A		intron_variant, NMD_transcript_variant		1
CDAN1	ENST00000643434.1	c.*1352+20G>A		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0214 AC: 3262 AN: 152208 Hom.: 102 Cov.: 33

Gnomad AFR AF: 0.0706

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0121

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00123

Gnomad OTH AF: 0.0230

GnomAD3 exomes AF: 0.00638 AC: 1599 AN: 250794 Hom.: 44 AF XY: 0.00498 AC XY: 676 AN XY: 135770

Gnomad AFR exome AF: 0.0700

Gnomad AMR exome AF: 0.00741

Gnomad ASJ exome AF: 0.00328

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00121

Gnomad OTH exome AF: 0.00637

GnomAD4 exome AF: 0.00297 AC: 4339 AN: 1461598 Hom.: 92 Cov.: 34 AF XY: 0.00267 AC XY: 1940 AN XY: 727108

Gnomad4 AFR exome AF: 0.0727

Gnomad4 AMR exome AF: 0.00776

Gnomad4 ASJ exome AF: 0.00253

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000104

Gnomad4 FIN exome AF: 0.0000936

Gnomad4 NFE exome AF: 0.000833

Gnomad4 OTH exome AF: 0.00795

GnomAD4 genome AF: 0.0216 AC: 3292 AN: 152326 Hom.: 105 Cov.: 33 AF XY: 0.0206 AC XY: 1534 AN XY: 74490

Gnomad4 AFR AF: 0.0712

Gnomad4 AMR AF: 0.0121

Gnomad4 ASJ AF: 0.00230

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00123

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.0157 Hom.: 18

Bravo AF: 0.0248

Asia WGS AF: 0.00722 AC: 25 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 26, 2024

- -

Anemia, congenital dyserythropoietic, type 1a Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Nov 03, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	2.8
Dann	Benign	0.62

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: rs75993383; hg19: chr15-43022776;