rs111961345

Variant names:

• chr15-42724025-TAAG-T
• rs111961345
• NM_138477.4:c.*463_*465delCTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_138477.4(CDAN1):​c.*463_*465delCTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0411 in 245,478 control chromosomes in the GnomAD database, including 660 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.056 (593 hom., cov: 32)
  • Exomes 𝑓: 0.017 (67 hom.)
• Consequence: CDAN1 NM_138477.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.67
• 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: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics
• congenital dyserythropoietic anemia type 1

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

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

ENSG00000278769 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 15-42724025-TAAG-T is Benign according to our data. Variant chr15-42724025-TAAG-T is described in ClinVar as Likely_benign. ClinVar VariationId is 315911.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.17 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.*463_*465delCTT		3_prime_UTR	Exon 28 of 28	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.*463_*465delCTT		3_prime_UTR	Exon 28 of 28	ENSP00000348564.3	Q8IWY9-2
	CDAN1	ENST00000562465.5	TSL:1	n.*1049_*1051delCTT		non_coding_transcript_exon	Exon 15 of 15	ENSP00000454246.1	H3BM60
	CDAN1	ENST00000562465.5	TSL:1	n.*1049_*1051delCTT		3_prime_UTR	Exon 15 of 15	ENSP00000454246.1	H3BM60

Frequencies

GnomAD3 genomes AF: 0.0559 AC: 8500 AN: 152120 Hom.: 591 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0215

Gnomad ASJ AF: 0.0297

Gnomad EAS AF: 0.0581

Gnomad SAS AF: 0.0280

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00510

Gnomad OTH AF: 0.0402

GnomAD4 exome AF: 0.0167 AC: 1559 AN: 93240 Hom.: 67 AF XY: 0.0178 AC XY: 873 AN XY: 49064

African (AFR) AF: 0.165 AC: 441 AN: 2666

American (AMR) AF: 0.0105 AC: 45 AN: 4288

Ashkenazi Jewish (ASJ) AF: 0.0306 AC: 66 AN: 2160

East Asian (EAS) AF: 0.0664 AC: 287 AN: 4322

South Asian (SAS) AF: 0.0287 AC: 411 AN: 14334

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4464

Middle Eastern (MID) AF: 0.0188 AC: 7 AN: 372

European-Non Finnish (NFE) AF: 0.00406 AC: 227 AN: 55906

Other (OTH) AF: 0.0159 AC: 75 AN: 4728

GnomAD4 genome AF: 0.0560 AC: 8519 AN: 152238 Hom.: 593 Cov.: 32 AF XY: 0.0541 AC XY: 4027 AN XY: 74458

African (AFR) AF: 0.174 AC: 7207 AN: 41502

American (AMR) AF: 0.0215 AC: 329 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0297 AC: 103 AN: 3472

East Asian (EAS) AF: 0.0583 AC: 302 AN: 5184

South Asian (SAS) AF: 0.0280 AC: 135 AN: 4824

European-Finnish (FIN) AF: 0.000565 AC: 6 AN: 10622

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00509 AC: 346 AN: 68022

Other (OTH) AF: 0.0402 AC: 85 AN: 2114

Alfa AF: 0.0333 Hom.: 46

Bravo AF: 0.0626

Asia WGS AF: 0.0470 AC: 164 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Congenital dyserythropoietic anemia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs111961345; hg19: chr15-43016223;