15-42724277-A-G

Variant names:

• chr15-42724277-A-G
• rs3742988
• ENST00000562465.5:n.*800T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000562465.5(CDAN1):​n.*800T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 590,932 control chromosomes in the GnomAD database, including 35,840 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (17635 hom., cov: 33)
  • Exomes 𝑓: 0.26 (18205 hom.)
• Consequence: CDAN1 ENST00000562465.5 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.43
• Publications: 7 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

ENSG00000278769 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 15-42724277-A-G is Benign according to our data. Variant chr15-42724277-A-G is described in ClinVar as Benign. ClinVar VariationId is 315915.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDAN1	NM_138477.4	c.*214T>C		3_prime_UTR_variant	Exon 28 of 28	ENST00000356231.4	NP_612486.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDAN1	ENST00000356231.4	c.*214T>C		3_prime_UTR_variant	Exon 28 of 28	1	NM_138477.4	ENSP00000348564.3

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59180 AN: 152052 Hom.: 17574 Cov.: 33

Gnomad AFR AF: 0.835

Gnomad AMI AF: 0.0923

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.339

GnomAD4 exome AF: 0.255 AC: 111889 AN: 438762 Hom.: 18205 Cov.: 5 AF XY: 0.265 AC XY: 61495 AN XY: 231874

African (AFR) AF: 0.840 AC: 10603 AN: 12624

American (AMR) AF: 0.145 AC: 3137 AN: 21708

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 3850 AN: 13074

East Asian (EAS) AF: 0.247 AC: 6604 AN: 26766

South Asian (SAS) AF: 0.434 AC: 20839 AN: 47982

European-Finnish (FIN) AF: 0.244 AC: 6199 AN: 25424

Middle Eastern (MID) AF: 0.286 AC: 521 AN: 1820

European-Non Finnish (NFE) AF: 0.202 AC: 53452 AN: 265038

Other (OTH) AF: 0.275 AC: 6684 AN: 24326

GnomAD4 genome AF: 0.390 AC: 59295 AN: 152170 Hom.: 17635 Cov.: 33 AF XY: 0.386 AC XY: 28748 AN XY: 74408

African (AFR) AF: 0.836 AC: 34708 AN: 41524

American (AMR) AF: 0.197 AC: 3007 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1040 AN: 3470

East Asian (EAS) AF: 0.251 AC: 1295 AN: 5168

South Asian (SAS) AF: 0.421 AC: 2034 AN: 4828

European-Finnish (FIN) AF: 0.237 AC: 2505 AN: 10588

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.203 AC: 13832 AN: 67984

Other (OTH) AF: 0.335 AC: 708 AN: 2112

Alfa AF: 0.258 Hom.: 9338

Bravo AF: 0.400

Asia WGS AF: 0.355 AC: 1234 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

May 10, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Congenital dyserythropoietic anemia, type I Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.2
DANN	Benign	0.51
PhyloP100		1.4
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: rs3742988; hg19: chr15-43016475;