rs7167392

Variant names:

• chr15-42736394-G-A
• rs7167392
• NM_138477.4:c.477C>T

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.477C>T​(p.Pro159Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 1,611,732 control chromosomes in the GnomAD database, including 45,844 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (5926 hom., cov: 32)
  • Exomes 𝑓: 0.23 (39918 hom.)
• Consequence: CDAN1 NM_138477.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.213
• 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: 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 15-42736394-G-A is Benign according to our data. Variant chr15-42736394-G-A is described in ClinVar as Benign. ClinVar VariationId is 262378.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.213 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.388 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDAN1	NM_138477.4	MANE Select	c.477C>T	p.Pro159Pro	synonymous	Exon 2 of 28	NP_612486.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDAN1	ENST00000356231.4	TSL:1 MANE Select	c.477C>T	p.Pro159Pro	synonymous	Exon 2 of 28	ENSP00000348564.3
	CDAN1	ENST00000643434.1		n.91-313C>T		intron	N/A	ENSP00000494699.1
	CDAN1	ENST00000563260.1	TSL:3	c.*168C>T		downstream_gene	N/A	ENSP00000455536.1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39689 AN: 151870 Hom.: 5923 Cov.: 32

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.0947

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.0640

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.240

GnomAD2 exomes AF: 0.225 AC: 54525 AN: 242160 AF XY: 0.234

Gnomad AFR exome AF: 0.403

Gnomad AMR exome AF: 0.113

Gnomad ASJ exome AF: 0.282

Gnomad EAS exome AF: 0.0639

Gnomad FIN exome AF: 0.247

Gnomad NFE exome AF: 0.214

Gnomad OTH exome AF: 0.221

GnomAD4 exome AF: 0.225 AC: 329005 AN: 1459744 Hom.: 39918 Cov.: 35 AF XY: 0.230 AC XY: 167136 AN XY: 726044

African (AFR) AF: 0.399 AC: 13350 AN: 33460

American (AMR) AF: 0.118 AC: 5290 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 7303 AN: 26098

East Asian (EAS) AF: 0.0876 AC: 3476 AN: 39674

South Asian (SAS) AF: 0.369 AC: 31766 AN: 86196

European-Finnish (FIN) AF: 0.252 AC: 13193 AN: 52422

Middle Eastern (MID) AF: 0.261 AC: 1504 AN: 5766

European-Non Finnish (NFE) AF: 0.215 AC: 239135 AN: 1111218

Other (OTH) AF: 0.232 AC: 13988 AN: 60250

GnomAD4 genome AF: 0.261 AC: 39709 AN: 151988 Hom.: 5926 Cov.: 32 AF XY: 0.262 AC XY: 19462 AN XY: 74308

African (AFR) AF: 0.393 AC: 16285 AN: 41472

American (AMR) AF: 0.157 AC: 2396 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 983 AN: 3468

East Asian (EAS) AF: 0.0641 AC: 330 AN: 5146

South Asian (SAS) AF: 0.354 AC: 1705 AN: 4822

European-Finnish (FIN) AF: 0.253 AC: 2678 AN: 10590

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.216 AC: 14688 AN: 67896

Other (OTH) AF: 0.236 AC: 498 AN: 2108

Alfa AF: 0.240 Hom.: 2094

Bravo AF: 0.257

Asia WGS AF: 0.206 AC: 715 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	not specified (3)
-	-	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	-0.79
CADD	Benign	9.9
DANN	Benign	0.93
PhyloP100		0.21
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: rs7167392; hg19: chr15-43028592; COSMIC: COSV51174689; COSMIC: COSV51174689;