chr15-36645260-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_032499.6(CDIN1):​c.-110C>T 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 0.00385 in 1,553,158 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0023 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0040 (13 hom.)
• Consequence: CDIN1 NM_032499.6 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.16
• Publications: 4 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: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004472494).
• BP6: Variant 15-36645260-C-T is Benign according to our data. Variant chr15-36645260-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 710471.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 13 AR gene

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>T	p.Ser62Leu	missense	Exon 3 of 11	NP_001308688.1	Q9Y2V0-1
	CDIN1	NM_001290232.2		c.-110C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 11	NP_001277161.1	Q9Y2V0-2
	CDIN1	NM_001321756.2		c.-110C>T		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>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 11	ENSP00000457854.1	Q9Y2V0-2
	CDIN1	ENST00000567389.5	TSL:1	c.-110C>T		5_prime_UTR_premature_start_codon_gain	Exon 4 of 12	ENSP00000456736.1	Q9Y2V0-2
	CDIN1	ENST00000566621.6	TSL:5 MANE Select	c.185C>T	p.Ser62Leu	missense	Exon 3 of 11	ENSP00000455397.1	Q9Y2V0-1

Frequencies

GnomAD3 genomes AF: 0.00230 AC: 350 AN: 152038 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000990

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000787

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00114

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00409

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00214 AC: 344 AN: 160848 AF XY: 0.00197

Gnomad AFR exome AF: 0.00114

Gnomad AMR exome AF: 0.000914

Gnomad ASJ exome AF: 0.00137

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00153

Gnomad NFE exome AF: 0.00425

Gnomad OTH exome AF: 0.00111

GnomAD4 exome AF: 0.00402 AC: 5631 AN: 1401002 Hom.: 13 Cov.: 32 AF XY: 0.00391 AC XY: 2700 AN XY: 691260

African (AFR) AF: 0.000820 AC: 26 AN: 31720

American (AMR) AF: 0.000803 AC: 29 AN: 36094

Ashkenazi Jewish (ASJ) AF: 0.00185 AC: 47 AN: 25358

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

South Asian (SAS) AF: 0.000101 AC: 8 AN: 79432

European-Finnish (FIN) AF: 0.00160 AC: 79 AN: 49378

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

European-Non Finnish (NFE) AF: 0.00491 AC: 5295 AN: 1079420

Other (OTH) AF: 0.00253 AC: 147 AN: 58072

GnomAD4 genome AF: 0.00230 AC: 350 AN: 152156 Hom.: 1 Cov.: 33 AF XY: 0.00222 AC XY: 165 AN XY: 74380

African (AFR) AF: 0.000988 AC: 41 AN: 41518

American (AMR) AF: 0.000786 AC: 12 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00114 AC: 12 AN: 10564

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00409 AC: 278 AN: 68012

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00337 Hom.: 0

Bravo AF: 0.00227

TwinsUK AF: 0.00458 AC: 17

ALSPAC AF: 0.00649 AC: 25

ESP6500AA AF: 0.00130 AC: 4

ESP6500EA AF: 0.00386 AC: 27

ExAC AF: 0.00105 AC: 108

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	CDIN1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	14
DANN	Benign	0.68
DEOGEN2	Benign	0.0063	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.0045	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.2
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.022
Sift	Benign	0.23	T
Sift4G	Benign	0.23	T
Polyphen		0.019	B
Vest4		0.15
MVP		0.14
MPC		0.12
ClinPred		0.00074	T
GERP RS		-0.34
Varity_R		0.050
gMVP		0.23
Mutation Taster		=98/2	polymorphism

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; COSMIC: COSV57713946; COSMIC: COSV57713946;