rs76599133

Variant names:

• chr15-42735637-G-T
• rs76599133
• NM_138477.4:c.816C>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_138477.4(CDAN1):​c.816C>A​(p.Thr272Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0175 in 1,614,048 control chromosomes in the GnomAD database, including 1,784 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.060 (776 hom., cov: 32)
  • Exomes 𝑓: 0.013 (1008 hom.)
• Consequence: CDAN1 NM_138477.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.228
• Publications: 6 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 15-42735637-G-T is Benign according to our data. Variant chr15-42735637-G-T is described in ClinVar as Benign. ClinVar VariationId is 262380.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.228 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 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.816C>A	p.Thr272Thr	synonymous	Exon 4 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.816C>A	p.Thr272Thr	synonymous	Exon 4 of 28	ENSP00000348564.3	Q8IWY9-2
	CDAN1	ENST00000913682.1		c.819C>A	p.Thr273Thr	synonymous	Exon 4 of 28	ENSP00000583741.1
	CDAN1	ENST00000913683.1		c.816C>A	p.Thr272Thr	synonymous	Exon 4 of 28	ENSP00000583742.1

Frequencies

GnomAD3 genomes AF: 0.0601 AC: 9137 AN: 152092 Hom.: 769 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0253

Gnomad ASJ AF: 0.00518

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.0365

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00315

Gnomad OTH AF: 0.0465

GnomAD2 exomes AF: 0.0299 AC: 7491 AN: 250348 AF XY: 0.0271

Gnomad AFR exome AF: 0.189

Gnomad AMR exome AF: 0.0145

Gnomad ASJ exome AF: 0.00578

Gnomad EAS exome AF: 0.128

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.00343

Gnomad OTH exome AF: 0.0157

GnomAD4 exome AF: 0.0131 AC: 19091 AN: 1461840 Hom.: 1008 Cov.: 32 AF XY: 0.0131 AC XY: 9529 AN XY: 727234

African (AFR) AF: 0.191 AC: 6402 AN: 33480

American (AMR) AF: 0.0165 AC: 738 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00520 AC: 136 AN: 26136

East Asian (EAS) AF: 0.104 AC: 4130 AN: 39700

South Asian (SAS) AF: 0.0345 AC: 2973 AN: 86258

European-Finnish (FIN) AF: 0.000300 AC: 16 AN: 53388

Middle Eastern (MID) AF: 0.0231 AC: 133 AN: 5766

European-Non Finnish (NFE) AF: 0.00270 AC: 3003 AN: 1111992

Other (OTH) AF: 0.0258 AC: 1560 AN: 60396

GnomAD4 genome AF: 0.0603 AC: 9172 AN: 152208 Hom.: 776 Cov.: 32 AF XY: 0.0588 AC XY: 4375 AN XY: 74432

African (AFR) AF: 0.184 AC: 7637 AN: 41484

American (AMR) AF: 0.0253 AC: 387 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00518 AC: 18 AN: 3472

East Asian (EAS) AF: 0.122 AC: 629 AN: 5176

South Asian (SAS) AF: 0.0365 AC: 176 AN: 4824

European-Finnish (FIN) AF: 0.000659 AC: 7 AN: 10624

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.00315 AC: 214 AN: 68016

Other (OTH) AF: 0.0456 AC: 96 AN: 2106

Alfa AF: 0.0322 Hom.: 187

Bravo AF: 0.0670

Asia WGS AF: 0.0810 AC: 282 AN: 3478

EpiCase AF: 0.00463

EpiControl AF: 0.00409

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	6.0
DANN	Benign	0.64
PhyloP100		0.23
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs76599133; hg19: chr15-43027835; COSMIC: COSV51177738; COSMIC: COSV51177738;