15-36644592-C-T

Variant names:

• chr15-36644592-C-T
• rs4923721
• NM_001321759.2:c.147+269C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_001321759.2(CDIN1):​c.147+269C>T variant causes a intron change. The variant allele was found at a frequency of 0.954 in 152,210 control chromosomes in the GnomAD database, including 69,260 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.95 (69260 hom., cov: 30)
• Consequence: CDIN1 NM_001321759.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.98
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 15-36644592-C-T is Benign according to our data. Variant chr15-36644592-C-T is described in ClinVar as Benign. ClinVar VariationId is 1294012.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDIN1	NM_001321759.2	MANE Select	c.147+269C>T		intron	N/A	NP_001308688.1	Q9Y2V0-1
	CDIN1	NM_001321761.2		c.147+269C>T		intron	N/A	NP_001308690.1	H3BS01
	CDIN1	NM_001290233.2		c.147+269C>T		intron	N/A	NP_001277162.1	A0A2R8YD89

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDIN1	ENST00000566621.6	TSL:5 MANE Select	c.147+269C>T		intron	N/A	ENSP00000455397.1	Q9Y2V0-1
	CDIN1	ENST00000437989.6	TSL:1	c.147+269C>T		intron	N/A	ENSP00000401362.2	Q9Y2V0-1
	CDIN1	ENST00000562877.5	TSL:1	c.-148+269C>T		intron	N/A	ENSP00000457854.1	Q9Y2V0-2

Frequencies

GnomAD3 genomes AF: 0.954 AC: 145100 AN: 152092 Hom.: 69221 Cov.: 30

Gnomad AFR AF: 0.935

Gnomad AMI AF: 0.942

Gnomad AMR AF: 0.952

Gnomad ASJ AF: 0.961

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.949

Gnomad FIN AF: 0.988

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.958

Gnomad OTH AF: 0.954

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.954 AC: 145196 AN: 152210 Hom.: 69260 Cov.: 30 AF XY: 0.956 AC XY: 71155 AN XY: 74420

African (AFR) AF: 0.935 AC: 38785 AN: 41498

American (AMR) AF: 0.953 AC: 14564 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.961 AC: 3338 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5153 AN: 5160

South Asian (SAS) AF: 0.949 AC: 4577 AN: 4824

European-Finnish (FIN) AF: 0.988 AC: 10487 AN: 10616

Middle Eastern (MID) AF: 0.949 AC: 279 AN: 294

European-Non Finnish (NFE) AF: 0.958 AC: 65141 AN: 68028

Other (OTH) AF: 0.951 AC: 2013 AN: 2116

Alfa AF: 0.957 Hom.: 24984

Bravo AF: 0.951

Asia WGS AF: 0.949 AC: 3301 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	18
DANN	Benign	0.77
PhyloP100		4.0
Mutation Taster		=97/3	polymorphism (auto)

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: rs4923721; hg19: chr15-36936793;