rs28661826

Variant names:

• chr15-42726361-C-T
• rs28661826
• NM_138477.4:c.3153G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-42726361-C-T
• chr15-42726361-C-A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_138477.4(CDAN1):​c.3153G>A​(p.Glu1051Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0221 in 1,598,168 control chromosomes in the GnomAD database, including 1,583 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.061 (649 hom., cov: 33)
  • Exomes 𝑓: 0.018 (934 hom.)
• Consequence: CDAN1 NM_138477.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.470
• Publications: 5 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

ENSG00000274403 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 15-42726361-C-T is Benign according to our data. Variant chr15-42726361-C-T is described in ClinVar as Benign. ClinVar VariationId is 262374.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.47 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.175 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.3153G>A	p.Glu1051Glu	synonymous	Exon 24 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.3153G>A	p.Glu1051Glu	synonymous	Exon 24 of 28	ENSP00000348564.3	Q8IWY9-2
	CDAN1	ENST00000562465.5	TSL:1	n.*55G>A		non_coding_transcript_exon	Exon 11 of 15	ENSP00000454246.1	H3BM60
	CDAN1	ENST00000562465.5	TSL:1	n.*55G>A		3_prime_UTR	Exon 11 of 15	ENSP00000454246.1	H3BM60

Frequencies

GnomAD3 genomes AF: 0.0613 AC: 9337 AN: 152216 Hom.: 647 Cov.: 33

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0243

Gnomad ASJ AF: 0.0351

Gnomad EAS AF: 0.0586

Gnomad SAS AF: 0.0457

Gnomad FIN AF: 0.00386

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0107

Gnomad OTH AF: 0.0454

GnomAD2 exomes AF: 0.0302 AC: 6660 AN: 220590 AF XY: 0.0292

Gnomad AFR exome AF: 0.179

Gnomad AMR exome AF: 0.0125

Gnomad ASJ exome AF: 0.0363

Gnomad EAS exome AF: 0.0654

Gnomad FIN exome AF: 0.00335

Gnomad NFE exome AF: 0.0105

Gnomad OTH exome AF: 0.0223

GnomAD4 exome AF: 0.0179 AC: 25941 AN: 1445834 Hom.: 934 Cov.: 33 AF XY: 0.0185 AC XY: 13266 AN XY: 717826

African (AFR) AF: 0.191 AC: 6317 AN: 33160

American (AMR) AF: 0.0149 AC: 632 AN: 42342

Ashkenazi Jewish (ASJ) AF: 0.0385 AC: 991 AN: 25718

East Asian (EAS) AF: 0.0509 AC: 1980 AN: 38870

South Asian (SAS) AF: 0.0473 AC: 3953 AN: 83562

European-Finnish (FIN) AF: 0.00359 AC: 187 AN: 52144

Middle Eastern (MID) AF: 0.0231 AC: 132 AN: 5706

European-Non Finnish (NFE) AF: 0.00919 AC: 10148 AN: 1104588

Other (OTH) AF: 0.0268 AC: 1601 AN: 59744

GnomAD4 genome AF: 0.0614 AC: 9358 AN: 152334 Hom.: 649 Cov.: 33 AF XY: 0.0598 AC XY: 4455 AN XY: 74498

African (AFR) AF: 0.179 AC: 7428 AN: 41566

American (AMR) AF: 0.0242 AC: 371 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0351 AC: 122 AN: 3472

East Asian (EAS) AF: 0.0587 AC: 304 AN: 5180

South Asian (SAS) AF: 0.0460 AC: 222 AN: 4830

European-Finnish (FIN) AF: 0.00386 AC: 41 AN: 10626

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0107 AC: 730 AN: 68030

Other (OTH) AF: 0.0449 AC: 95 AN: 2114

Alfa AF: 0.0267 Hom.: 72

Bravo AF: 0.0673

Asia WGS AF: 0.0540 AC: 190 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	not specified (3)
-	-	1	Anemia, congenital dyserythropoietic, type 1a (1)
-	-	1	Congenital dyserythropoietic anemia, type I (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	5.2
DANN	Benign	0.48
PhyloP100		-0.47
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: rs28661826; hg19: chr15-43018559;