15-36654102-C-A

Position:

• chr15-36654102-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032499.6(CDIN1):​c.-78C>A variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.0000154 in 1,423,980 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: 31)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: CDIN1 NM_032499.6 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.70

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35504982).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDIN1	NM_001321759.2	c.217C>A	p.Leu73Met	missense_variant	4/11	ENST00000566621.6	NP_001308688.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDIN1	ENST00000566621.6	c.217C>A	p.Leu73Met	missense_variant	4/11	5	NM_001321759.2	ENSP00000455397.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.0000154 AC: 22 AN: 1423980 Hom.: 0 Cov.: 33 AF XY: 0.0000156 AC XY: 11 AN XY: 704378

Gnomad4 AFR exome AF: 0.0000303

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000260

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000183

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.013	T;.;.;.;T;.;T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.84	.;T;T;T;.;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.36	T;T;T;T;T;T;T
MetaSVM	Benign	-0.61	T
MutationAssessor	Uncertain	2.2	M;.;.;.;M;.;M
PROVEAN	Benign	-0.40	N;.;N;N;.;.;N
REVEL	Benign	0.11
Sift	Benign	0.052	T;.;D;D;.;.;T
Sift4G	Benign	0.076	T;.;D;T;.;.;T
Polyphen		0.99	D;.;.;.;D;.;D
Vest4		0.34
MutPred		0.27		Gain of catalytic residue at L73 (P = 0.0372);Gain of catalytic residue at L73 (P = 0.0372);.;Gain of catalytic residue at L73 (P = 0.0372);Gain of catalytic residue at L73 (P = 0.0372);Gain of catalytic residue at L73 (P = 0.0372);Gain of catalytic residue at L73 (P = 0.0372);
MVP		0.35
MPC		0.56
ClinPred		0.90	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.28

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

Publications

LitVar

Other links and lift over

dbSNP: rs3784678; hg19: chr15-36946303; COSMIC: COSV57712967;