NM_138477.4:c.2174+20G>A

Variant names:

• chr15-42730578-C-T
• rs75993383
• NM_138477.4:c.2174+20G>A

Variant summary

Our verdict is Benign. The variant received -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:4
• Conservation: PhyloP100: -0.299
• Publications: 1 publications found

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]

CDAN1 Gene-Disease associations (from GenCC):

• anemia, congenital dyserythropoietic, type 1a

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
• congenital dyserythropoietic anemia type 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• congenital dyserythropoietic anemia

  Inheritance: AR Classification: LIMITED Submitted by: Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138477.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDAN1	NM_138477.4	MANE Select	c.2174+20G>A		intron	N/A	NP_612486.2	Q8IWY9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDAN1	ENST00000356231.4	TSL:1 MANE Select	c.2174+20G>A		intron	N/A	ENSP00000348564.3	Q8IWY9-2
	CDAN1	ENST00000562465.5	TSL:1	n.167+20G>A		intron	N/A	ENSP00000454246.1	H3BM60
	CDAN1	ENST00000913682.1		c.2177+20G>A		intron	N/A	ENSP00000583741.1

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

GnomAD2 exomes AF: 0.00638 AC: 1599 AN: 250794 AF XY: 0.00498

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 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

African (AFR) AF: 0.0727 AC: 2434 AN: 33464

American (AMR) AF: 0.00776 AC: 347 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00253 AC: 66 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86220

European-Finnish (FIN) AF: 0.0000936 AC: 5 AN: 53412

Middle Eastern (MID) AF: 0.0123 AC: 71 AN: 5764

European-Non Finnish (NFE) AF: 0.000833 AC: 926 AN: 1111836

Other (OTH) AF: 0.00795 AC: 480 AN: 60374

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

African (AFR) AF: 0.0712 AC: 2957 AN: 41554

American (AMR) AF: 0.0121 AC: 185 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00230 AC: 8 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.00123 AC: 84 AN: 68036

Other (OTH) AF: 0.0227 AC: 48 AN: 2112

Alfa AF: 0.0136 Hom.: 21

Bravo AF: 0.0248

Asia WGS AF: 0.00722 AC: 25 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Anemia, congenital dyserythropoietic, type 1a (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.8
DANN	Benign	0.62
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs75993383; hg19: chr15-43022776;