15-36692111-C-G

Variant names:

• chr15-36692111-C-G
• rs139444685
• NM_001321759.2:c.427-15C>G

Variant summary

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

The NM_001321759.2(CDIN1):​c.427-15C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00411 in 1,613,218 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 0.0031 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0042 (14 hom.)
• Consequence: CDIN1 NM_001321759.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.48
• 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

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 15-36692111-C-G is Benign according to our data. Variant chr15-36692111-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 257534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 14 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321759.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDIN1	NM_001321759.2	MANE Select	c.427-15C>G		intron	N/A	NP_001308688.1
	CDIN1	NM_001321761.2		c.427-15C>G		intron	N/A	NP_001308690.1
	CDIN1	NM_001290233.2		c.427-15C>G		intron	N/A	NP_001277162.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDIN1	ENST00000566621.6	TSL:5 MANE Select	c.427-15C>G		intron	N/A	ENSP00000455397.1
	CDIN1	ENST00000437989.6	TSL:1	c.427-15C>G		intron	N/A	ENSP00000401362.2
	CDIN1	ENST00000562877.5	TSL:1	c.133-15C>G		intron	N/A	ENSP00000457854.1

Frequencies

GnomAD3 genomes AF: 0.00313 AC: 476 AN: 152116 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000821

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.000755

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00544

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.00273 AC: 679 AN: 248568 AF XY: 0.00272

Gnomad AFR exome AF: 0.000907

Gnomad AMR exome AF: 0.00250

Gnomad ASJ exome AF: 0.00468

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000606

Gnomad NFE exome AF: 0.00420

Gnomad OTH exome AF: 0.00298

GnomAD4 exome AF: 0.00422 AC: 6161 AN: 1460984 Hom.: 14 Cov.: 31 AF XY: 0.00415 AC XY: 3016 AN XY: 726778

African (AFR) AF: 0.000598 AC: 20 AN: 33448

American (AMR) AF: 0.00289 AC: 129 AN: 44646

Ashkenazi Jewish (ASJ) AF: 0.00563 AC: 147 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.000835 AC: 72 AN: 86200

European-Finnish (FIN) AF: 0.000619 AC: 33 AN: 53324

Middle Eastern (MID) AF: 0.00243 AC: 14 AN: 5764

European-Non Finnish (NFE) AF: 0.00498 AC: 5532 AN: 1111482

Other (OTH) AF: 0.00355 AC: 214 AN: 60328

GnomAD4 genome AF: 0.00313 AC: 476 AN: 152234 Hom.: 0 Cov.: 31 AF XY: 0.00284 AC XY: 211 AN XY: 74426

African (AFR) AF: 0.000819 AC: 34 AN: 41532

American (AMR) AF: 0.00229 AC: 35 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00403 AC: 14 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4828

European-Finnish (FIN) AF: 0.000755 AC: 8 AN: 10602

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00544 AC: 370 AN: 68018

Other (OTH) AF: 0.00378 AC: 8 AN: 2114

Alfa AF: 0.00501 Hom.: 0

Bravo AF: 0.00327

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Jan 22, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	16
DANN	Benign	0.44
PhyloP100		3.5
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs139444685; hg19: chr15-36984312;