rs139465273

Variant names:

• chr15-36645260-C-G
• rs139465273
• ENST00000562877.5:c.-110C>G

Your query was ambiguous. Multiple possible variants found:

• chr15-36645260-C-G
• chr15-36645260-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032499.6(CDIN1):​c.-110C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000714 in 1,401,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: CDIN1 NM_032499.6 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16
• Publications: 0 publications found

Genes affected

CDIN1 (HGNC:26929): (CDAN1 interacting nuclease 1) This gene encodes a protein with two predicted helix-turn-helix domains. Mutations in this gene were found in families with congenital dyserythropoietic anemia type Ib. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2014]

CDIN1 Gene-Disease associations (from GenCC):

• congenital dyserythropoietic anemia type type 1B

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• congenital dyserythropoietic anemia type 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000261191 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.120535195).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032499.6. 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
	CDIN1	NM_001321759.2	MANE Select	c.185C>G	p.Ser62Trp	missense	Exon 3 of 11	NP_001308688.1	Q9Y2V0-1
	CDIN1	NM_001290232.2		c.-110C>G		5_prime_UTR_premature_start_codon_gain	Exon 3 of 11	NP_001277161.1	Q9Y2V0-2
	CDIN1	NM_001321756.2		c.-110C>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 10	NP_001308685.1	Q9Y2V0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDIN1	ENST00000562877.5	TSL:1	c.-110C>G		5_prime_UTR_premature_start_codon_gain	Exon 3 of 11	ENSP00000457854.1	Q9Y2V0-2
	CDIN1	ENST00000567389.5	TSL:1	c.-110C>G		5_prime_UTR_premature_start_codon_gain	Exon 4 of 12	ENSP00000456736.1	Q9Y2V0-2
	CDIN1	ENST00000566621.6	TSL:5 MANE Select	c.185C>G	p.Ser62Trp	missense	Exon 3 of 11	ENSP00000455397.1	Q9Y2V0-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.14e-7 AC: 1 AN: 1401134 Hom.: 0 Cov.: 32 AF XY: 0.00000145 AC XY: 1 AN XY: 691332

African (AFR) AF: 0.00 AC: 0 AN: 31720

American (AMR) AF: 0.00 AC: 0 AN: 36094

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25360

East Asian (EAS) AF: 0.00 AC: 0 AN: 36078

South Asian (SAS) AF: 0.00 AC: 0 AN: 79432

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5450

European-Non Finnish (NFE) AF: 9.26e-7 AC: 1 AN: 1079546

Other (OTH) AF: 0.00 AC: 0 AN: 58076

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.67	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.2
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.12
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.013	D
Polyphen		0.89	P
Vest4		0.38
MutPred		0.30		Loss of disorder (P = 0.0015)
MVP		0.26
MPC		0.36
ClinPred		0.22	T
GERP RS		-0.34
Varity_R		0.099
gMVP		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs139465273; hg19: chr15-36937461;