rs139809959

Variant names:

• chr15-42729307-C-T
• rs139809959
• NM_138477.4:c.2463G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-42729307-C-T
• chr15-42729307-C-G

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_138477.4(CDAN1):​c.2463G>A​(p.Gly821Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0014 in 1,614,096 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0020 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0013 (8 hom.)
• Consequence: CDAN1 NM_138477.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.463
• Publications: 0 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP6: Variant 15-42729307-C-T is Benign according to our data. Variant chr15-42729307-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 262372.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.463 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00204 (311/152216) while in subpopulation AMR AF = 0.00458 (70/15290). AF 95% confidence interval is 0.00372. There are 1 homozygotes in GnomAd4. There are 134 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 8 AR gene

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.2463G>A	p.Gly821Gly	synonymous	Exon 18 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.2463G>A	p.Gly821Gly	synonymous	Exon 18 of 28	ENSP00000348564.3	Q8IWY9-2
	CDAN1	ENST00000562465.5	TSL:1	n.456G>A		non_coding_transcript_exon	Exon 5 of 15	ENSP00000454246.1	H3BM60
	CDAN1	ENST00000913682.1		c.2466G>A	p.Gly822Gly	synonymous	Exon 18 of 28	ENSP00000583741.1

Frequencies

GnomAD3 genomes AF: 0.00205 AC: 312 AN: 152098 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00249

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00458

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00162

Gnomad OTH AF: 0.00621

GnomAD2 exomes AF: 0.00163 AC: 409 AN: 250858 AF XY: 0.00154

Gnomad AFR exome AF: 0.00249

Gnomad AMR exome AF: 0.00419

Gnomad ASJ exome AF: 0.000596

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00166

Gnomad OTH exome AF: 0.00425

GnomAD4 exome AF: 0.00133 AC: 1949 AN: 1461880 Hom.: 8 Cov.: 42 AF XY: 0.00130 AC XY: 944 AN XY: 727242

African (AFR) AF: 0.00197 AC: 66 AN: 33480

American (AMR) AF: 0.00452 AC: 202 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000727 AC: 19 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86258

European-Finnish (FIN) AF: 0.000168 AC: 9 AN: 53416

Middle Eastern (MID) AF: 0.00798 AC: 46 AN: 5768

European-Non Finnish (NFE) AF: 0.00129 AC: 1430 AN: 1112002

Other (OTH) AF: 0.00277 AC: 167 AN: 60396

GnomAD4 genome AF: 0.00204 AC: 311 AN: 152216 Hom.: 1 Cov.: 31 AF XY: 0.00180 AC XY: 134 AN XY: 74406

African (AFR) AF: 0.00246 AC: 102 AN: 41526

American (AMR) AF: 0.00458 AC: 70 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.00162 AC: 110 AN: 68002

Other (OTH) AF: 0.00615 AC: 13 AN: 2114

Alfa AF: 0.00164 Hom.: 2

Bravo AF: 0.00252

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00169

EpiControl AF: 0.00202

ClinVar

ClinVar submissions

Significance: Benign/Likely 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	-0.33
CADD	Benign	8.5
DANN	Benign	0.67
PhyloP100		0.46
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs139809959; hg19: chr15-43021505;