rs12594483

Variant names:

• chr15-42729788-G-A
• rs12594483
• NM_138477.4:c.2352+8C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-42729788-G-A
• chr15-42729788-G-C

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.2352+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 1,610,632 control chromosomes in the GnomAD database, including 44,104 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.33 (15611 hom., cov: 31)
  • Exomes 𝑓: 0.15 (28493 hom.)
• Consequence: CDAN1 NM_138477.4 splice_region, intron
• Scores: Splicing: ADA: 0.00001100
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.299
• Publications: 25 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=-0.85).
• BP6: Variant 15-42729788-G-A is Benign according to our data. Variant chr15-42729788-G-A is described in ClinVar as Benign. ClinVar VariationId is 262370.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.814 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.2352+8C>T		splice_region 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.2352+8C>T		splice_region intron	N/A	ENSP00000348564.3	Q8IWY9-2
	CDAN1	ENST00000562465.5	TSL:1	n.345+8C>T		splice_region intron	N/A	ENSP00000454246.1	H3BM60
	CDAN1	ENST00000913682.1		c.2355+8C>T		splice_region intron	N/A	ENSP00000583741.1

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50396 AN: 151906 Hom.: 15548 Cov.: 31

Gnomad AFR AF: 0.820

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.287

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.282

GnomAD2 exomes AF: 0.209 AC: 52300 AN: 250466 AF XY: 0.203

Gnomad AFR exome AF: 0.832

Gnomad AMR exome AF: 0.132

Gnomad ASJ exome AF: 0.199

Gnomad EAS exome AF: 0.299

Gnomad FIN exome AF: 0.158

Gnomad NFE exome AF: 0.115

Gnomad OTH exome AF: 0.172

GnomAD4 exome AF: 0.153 AC: 223779 AN: 1458608 Hom.: 28493 Cov.: 33 AF XY: 0.156 AC XY: 113449 AN XY: 725720

African (AFR) AF: 0.851 AC: 28357 AN: 33330

American (AMR) AF: 0.139 AC: 6213 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 5094 AN: 26088

East Asian (EAS) AF: 0.286 AC: 11361 AN: 39664

South Asian (SAS) AF: 0.311 AC: 26771 AN: 86012

European-Finnish (FIN) AF: 0.164 AC: 8761 AN: 53382

Middle Eastern (MID) AF: 0.183 AC: 1034 AN: 5650

European-Non Finnish (NFE) AF: 0.112 AC: 124450 AN: 1109550

Other (OTH) AF: 0.195 AC: 11738 AN: 60270

GnomAD4 genome AF: 0.332 AC: 50522 AN: 152024 Hom.: 15611 Cov.: 31 AF XY: 0.329 AC XY: 24449 AN XY: 74306

African (AFR) AF: 0.821 AC: 34022 AN: 41444

American (AMR) AF: 0.178 AC: 2718 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 701 AN: 3468

East Asian (EAS) AF: 0.288 AC: 1486 AN: 5158

South Asian (SAS) AF: 0.307 AC: 1477 AN: 4816

European-Finnish (FIN) AF: 0.158 AC: 1668 AN: 10576

Middle Eastern (MID) AF: 0.192 AC: 56 AN: 292

European-Non Finnish (NFE) AF: 0.115 AC: 7801 AN: 67960

Other (OTH) AF: 0.279 AC: 588 AN: 2108

Alfa AF: 0.175 Hom.: 14743

Bravo AF: 0.353

Asia WGS AF: 0.325 AC: 1132 AN: 3478

EpiCase AF: 0.115

EpiControl AF: 0.118

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	-0.85
CADD	Benign	0.70
DANN	Benign	0.48
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000011
dbscSNV1_RF	Benign	0.0
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: rs12594483; hg19: chr15-43021986;