15-36654102-C-G

Variant names:

• chr15-36654102-C-G
• rs3784678
• NM_001321759.2:c.217C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001321761.2(CDIN1):​c.217C>G​(p.Leu73Val) variant causes a missense change. The variant allele was found at a frequency of 0.472 in 1,573,246 control chromosomes in the GnomAD database, including 177,965 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (15284 hom., cov: 31)
  • Exomes 𝑓: 0.47 (162681 hom.)
• Consequence: CDIN1 NM_001321761.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 3.70
• Publications: 36 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.810986E-5).
• BP6: Variant 15-36654102-C-G is Benign according to our data. Variant chr15-36654102-C-G is described in ClinVar as Benign. ClinVar VariationId is 257532.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321761.2. 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.217C>G	p.Leu73Val	missense	Exon 4 of 11	NP_001308688.1
	CDIN1	NM_001321761.2		c.217C>G	p.Leu73Val	missense	Exon 4 of 11	NP_001308690.1
	CDIN1	NM_001290233.2		c.217C>G	p.Leu73Val	missense	Exon 4 of 11	NP_001277162.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDIN1	ENST00000566621.6	TSL:5 MANE Select	c.217C>G	p.Leu73Val	missense	Exon 4 of 11	ENSP00000455397.1
	CDIN1	ENST00000437989.6	TSL:1	c.217C>G	p.Leu73Val	missense	Exon 4 of 12	ENSP00000401362.2
	CDIN1	ENST00000562877.5	TSL:1	c.-78C>G		5_prime_UTR	Exon 4 of 11	ENSP00000457854.1

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67364 AN: 151788 Hom.: 15280 Cov.: 31

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.653

Gnomad SAS AF: 0.595

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.467

Gnomad OTH AF: 0.434

GnomAD2 exomes AF: 0.462 AC: 89872 AN: 194482 AF XY: 0.473

Gnomad AFR exome AF: 0.380

Gnomad AMR exome AF: 0.347

Gnomad ASJ exome AF: 0.441

Gnomad EAS exome AF: 0.651

Gnomad FIN exome AF: 0.423

Gnomad NFE exome AF: 0.455

Gnomad OTH exome AF: 0.444

GnomAD4 exome AF: 0.475 AC: 674933 AN: 1421340 Hom.: 162681 Cov.: 33 AF XY: 0.479 AC XY: 336490 AN XY: 703086

African (AFR) AF: 0.393 AC: 12947 AN: 32946

American (AMR) AF: 0.350 AC: 13775 AN: 39352

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 11248 AN: 25542

East Asian (EAS) AF: 0.674 AC: 25886 AN: 38392

South Asian (SAS) AF: 0.589 AC: 47774 AN: 81062

European-Finnish (FIN) AF: 0.436 AC: 22263 AN: 51072

Middle Eastern (MID) AF: 0.479 AC: 2739 AN: 5716

European-Non Finnish (NFE) AF: 0.469 AC: 510675 AN: 1088328

Other (OTH) AF: 0.469 AC: 27626 AN: 58930

GnomAD4 genome AF: 0.444 AC: 67397 AN: 151906 Hom.: 15284 Cov.: 31 AF XY: 0.445 AC XY: 33067 AN XY: 74250

African (AFR) AF: 0.395 AC: 16340 AN: 41398

American (AMR) AF: 0.360 AC: 5492 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 1528 AN: 3472

East Asian (EAS) AF: 0.653 AC: 3363 AN: 5154

South Asian (SAS) AF: 0.596 AC: 2875 AN: 4824

European-Finnish (FIN) AF: 0.428 AC: 4511 AN: 10546

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.467 AC: 31745 AN: 67934

Other (OTH) AF: 0.435 AC: 917 AN: 2110

Alfa AF: 0.457 Hom.: 11605

Bravo AF: 0.434

TwinsUK AF: 0.459 AC: 1703

ALSPAC AF: 0.476 AC: 1834

ESP6500AA AF: 0.396 AC: 1239

ESP6500EA AF: 0.459 AC: 3286

ExAC AF: 0.413 AC: 48449

Asia WGS AF: 0.572 AC: 1987 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Congenital dyserythropoietic anemia type type 1B (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.82	T
MetaRNN	Benign	0.000028	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		3.7
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.15
Sift	Benign	0.079	T
Sift4G	Benign	0.098	T
Polyphen		0.88	P
Vest4		0.20
MPC		0.41
ClinPred		0.0098	T
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.18
gMVP		0.36
Mutation Taster		=200/100	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: rs3784678; hg19: chr15-36946303; COSMIC: COSV57713331;