rs12905385

Variant names:

• chr15-42729365-G-A
• rs12905385
• NM_138477.4:c.2408-3C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-42729365-G-A
• chr15-42729365-G-T

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.2408-3C>T variant causes a splice region, intron change. The variant allele was found at a frequency of 0.204 in 1,613,582 control chromosomes in the GnomAD database, including 37,050 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 0.24 (5076 hom., cov: 32)
  • Exomes 𝑓: 0.20 (31974 hom.)
• Consequence: CDAN1 NM_138477.4 splice_region, intron
• Scores: Splicing: ADA: 0.003605
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 6.03
• Publications: 15 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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 15-42729365-G-A is Benign according to our data. Variant chr15-42729365-G-A is described in ClinVar as Benign. ClinVar VariationId is 262371.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.371 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.2408-3C>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.2408-3C>T		splice_region intron	N/A	ENSP00000348564.3	Q8IWY9-2
	CDAN1	ENST00000562465.5	TSL:1	n.401-3C>T		splice_region intron	N/A	ENSP00000454246.1	H3BM60
	CDAN1	ENST00000913682.1		c.2411-3C>T		splice_region intron	N/A	ENSP00000583741.1

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36270 AN: 152010 Hom.: 5075 Cov.: 32

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.0545

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.221

GnomAD2 exomes AF: 0.201 AC: 50428 AN: 250652 AF XY: 0.209

Gnomad AFR exome AF: 0.381

Gnomad AMR exome AF: 0.0934

Gnomad ASJ exome AF: 0.252

Gnomad EAS exome AF: 0.0562

Gnomad FIN exome AF: 0.228

Gnomad NFE exome AF: 0.186

Gnomad OTH exome AF: 0.204

GnomAD4 exome AF: 0.200 AC: 292280 AN: 1461454 Hom.: 31974 Cov.: 42 AF XY: 0.204 AC XY: 148518 AN XY: 727038

African (AFR) AF: 0.379 AC: 12672 AN: 33466

American (AMR) AF: 0.0992 AC: 4435 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 6579 AN: 26132

East Asian (EAS) AF: 0.0699 AC: 2774 AN: 39700

South Asian (SAS) AF: 0.338 AC: 29155 AN: 86244

European-Finnish (FIN) AF: 0.232 AC: 12390 AN: 53412

Middle Eastern (MID) AF: 0.227 AC: 1306 AN: 5762

European-Non Finnish (NFE) AF: 0.189 AC: 210287 AN: 1111648

Other (OTH) AF: 0.210 AC: 12682 AN: 60372

GnomAD4 genome AF: 0.239 AC: 36292 AN: 152128 Hom.: 5076 Cov.: 32 AF XY: 0.239 AC XY: 17759 AN XY: 74370

African (AFR) AF: 0.376 AC: 15584 AN: 41456

American (AMR) AF: 0.136 AC: 2078 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 899 AN: 3470

East Asian (EAS) AF: 0.0548 AC: 284 AN: 5184

South Asian (SAS) AF: 0.323 AC: 1556 AN: 4824

European-Finnish (FIN) AF: 0.230 AC: 2441 AN: 10596

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.189 AC: 12881 AN: 67992

Other (OTH) AF: 0.219 AC: 462 AN: 2106

Alfa AF: 0.202 Hom.: 5446

Bravo AF: 0.234

Asia WGS AF: 0.194 AC: 674 AN: 3478

EpiCase AF: 0.186

EpiControl AF: 0.189

ClinVar

ClinVar submissions as Germline

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	-0.47
CADD	Benign	13
DANN	Benign	0.67
PhyloP100		6.0
Mutation Taster		=92/8	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0036
dbscSNV1_RF	Benign	0.12
SpliceAI score (max)		0.020		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: rs12905385; hg19: chr15-43021563; COSMIC: COSV62332280; COSMIC: COSV62332280;