rs10518893

Variant names:

• chr15-36605626-A-G
• rs10518893
• NM_001321759.2:c.101+25665A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001321759.2(CDIN1):​c.101+25665A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0397 in 152,310 control chromosomes in the GnomAD database, including 178 homozygotes. 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: 𝑓 0.040 (178 hom., cov: 32)
• Consequence: CDIN1 NM_001321759.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.119
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDIN1	NM_001321759.2	c.101+25665A>G		intron_variant	Intron 1 of 10	ENST00000566621.6	NP_001308688.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDIN1	ENST00000566621.6	c.101+25665A>G		intron_variant	Intron 1 of 10	5	NM_001321759.2	ENSP00000455397.1

Frequencies

GnomAD3 genomes AF: 0.0397 AC: 6040 AN: 152192 Hom.: 180 Cov.: 32

Gnomad AFR AF: 0.0276

Gnomad AMI AF: 0.0330

Gnomad AMR AF: 0.0253

Gnomad ASJ AF: 0.0109

Gnomad EAS AF: 0.0237

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.0379

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0464

Gnomad OTH AF: 0.0335

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

GnomAD4 genome AF: 0.0397 AC: 6042 AN: 152310 Hom.: 178 Cov.: 32 AF XY: 0.0406 AC XY: 3024 AN XY: 74468

African (AFR) AF: 0.0276 AC: 1148 AN: 41578

American (AMR) AF: 0.0252 AC: 386 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0109 AC: 38 AN: 3472

East Asian (EAS) AF: 0.0237 AC: 123 AN: 5182

South Asian (SAS) AF: 0.141 AC: 680 AN: 4822

European-Finnish (FIN) AF: 0.0379 AC: 402 AN: 10614

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0464 AC: 3158 AN: 68024

Other (OTH) AF: 0.0341 AC: 72 AN: 2114

Alfa AF: 0.0419 Hom.: 277

Bravo AF: 0.0352

Asia WGS AF: 0.0930 AC: 323 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	11
DANN	Benign	0.76
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10518893; hg19: chr15-36897827;