rs56046122

Variant names:

• chr15-42725478-G-A
• rs56046122
• NM_138477.4:c.3450+11C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-42725478-G-A
• chr15-42725478-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.3450+11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0213 in 1,614,006 control chromosomes in the GnomAD database, including 1,547 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.060 (631 hom., cov: 32)
  • Exomes 𝑓: 0.017 (916 hom.)
• Consequence: CDAN1 NM_138477.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -2.02
• Publications: 4 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=-0.96).
• BP6: Variant 15-42725478-G-A is Benign according to our data. Variant chr15-42725478-G-A is described in ClinVar as Benign. ClinVar VariationId is 262375.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.173 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.3450+11C>T		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.3450+11C>T		intron	N/A	ENSP00000348564.3	Q8IWY9-2
	CDAN1	ENST00000562465.5	TSL:1	n.*352+11C>T		intron	N/A	ENSP00000454246.1	H3BM60
	CDAN1	ENST00000913682.1		c.3453+11C>T		intron	N/A	ENSP00000583741.1

Frequencies

GnomAD3 genomes AF: 0.0603 AC: 9171 AN: 152088 Hom.: 629 Cov.: 32

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0240

Gnomad ASJ AF: 0.0340

Gnomad EAS AF: 0.0591

Gnomad SAS AF: 0.0427

Gnomad FIN AF: 0.00396

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0103

Gnomad OTH AF: 0.0450

GnomAD2 exomes AF: 0.0298 AC: 7480 AN: 251044 AF XY: 0.0282

Gnomad AFR exome AF: 0.177

Gnomad AMR exome AF: 0.0121

Gnomad ASJ exome AF: 0.0335

Gnomad EAS exome AF: 0.0661

Gnomad FIN exome AF: 0.00333

Gnomad NFE exome AF: 0.0103

Gnomad OTH exome AF: 0.0214

GnomAD4 exome AF: 0.0173 AC: 25248 AN: 1461800 Hom.: 916 Cov.: 32 AF XY: 0.0178 AC XY: 12928 AN XY: 727218

African (AFR) AF: 0.188 AC: 6292 AN: 33474

American (AMR) AF: 0.0143 AC: 638 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0367 AC: 960 AN: 26136

East Asian (EAS) AF: 0.0517 AC: 2052 AN: 39700

South Asian (SAS) AF: 0.0444 AC: 3828 AN: 86256

European-Finnish (FIN) AF: 0.00352 AC: 188 AN: 53396

Middle Eastern (MID) AF: 0.0229 AC: 132 AN: 5768

European-Non Finnish (NFE) AF: 0.00864 AC: 9602 AN: 1111956

Other (OTH) AF: 0.0258 AC: 1556 AN: 60390

GnomAD4 genome AF: 0.0604 AC: 9192 AN: 152206 Hom.: 631 Cov.: 32 AF XY: 0.0587 AC XY: 4367 AN XY: 74430

African (AFR) AF: 0.176 AC: 7311 AN: 41518

American (AMR) AF: 0.0240 AC: 367 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0340 AC: 118 AN: 3470

East Asian (EAS) AF: 0.0592 AC: 306 AN: 5170

South Asian (SAS) AF: 0.0429 AC: 207 AN: 4826

European-Finnish (FIN) AF: 0.00396 AC: 42 AN: 10614

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

European-Non Finnish (NFE) AF: 0.0103 AC: 702 AN: 68004

Other (OTH) AF: 0.0445 AC: 94 AN: 2112

Alfa AF: 0.0343 Hom.: 488

Bravo AF: 0.0662

Asia WGS AF: 0.0510 AC: 178 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	2	not specified (2)
-	-	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	-0.96
CADD	Benign	2.6
DANN	Benign	0.46
PhyloP100		-2.0
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: rs56046122; hg19: chr15-43017676;