chr15-42724277-A-G

Variant names:

• chr15-42724277-A-G
• rs3742988
• NM_138477.4:c.*214T>C

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.*214T>C variant causes a 3 prime UTR 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 NM_138477.4 3_prime_UTR
• 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: 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

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.

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.*214T>C		3_prime_UTR	Exon 28 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.*214T>C		3_prime_UTR	Exon 28 of 28	ENSP00000348564.3	Q8IWY9-2
	CDAN1	ENST00000562465.5	TSL:1	n.*800T>C		non_coding_transcript_exon	Exon 15 of 15	ENSP00000454246.1	H3BM60
	CDAN1	ENST00000562465.5	TSL:1	n.*800T>C		3_prime_UTR	Exon 15 of 15	ENSP00000454246.1	H3BM60

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Congenital dyserythropoietic anemia, type I (1)

Computational scores

Source: dbNSFP v4.9

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;