rs117638434

Variant names:

• chr15-36697377-C-T
• rs117638434
• NM_001321759.2:c.531C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-36697377-C-T
• chr15-36697377-C-A
• chr15-36697377-C-G

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_001321759.2(CDIN1):​c.531C>T​(p.Asn177Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0121 in 1,611,544 control chromosomes in the GnomAD database, including 178 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (12 hom., cov: 32)
  • Exomes 𝑓: 0.012 (166 hom.)
• Consequence: CDIN1 NM_001321759.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.06
• Publications: 3 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 15-36697377-C-T is Benign according to our data. Variant chr15-36697377-C-T is described in ClinVar as Benign. ClinVar VariationId is 257535.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.06 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 12 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDIN1	NM_001321759.2	MANE Select	c.531C>T	p.Asn177Asn	synonymous	Exon 8 of 11	NP_001308688.1	Q9Y2V0-1
	CDIN1	NM_001321761.2		c.531C>T	p.Asn177Asn	synonymous	Exon 8 of 11	NP_001308690.1	H3BS01
	CDIN1	NM_001290233.2		c.531C>T	p.Asn177Asn	synonymous	Exon 8 of 11	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.531C>T	p.Asn177Asn	synonymous	Exon 8 of 11	ENSP00000455397.1	Q9Y2V0-1
	CDIN1	ENST00000437989.6	TSL:1	c.531C>T	p.Asn177Asn	synonymous	Exon 8 of 12	ENSP00000401362.2	Q9Y2V0-1
	CDIN1	ENST00000562877.5	TSL:1	c.237C>T	p.Asn79Asn	synonymous	Exon 8 of 11	ENSP00000457854.1	Q9Y2V0-2

Frequencies

GnomAD3 genomes AF: 0.0101 AC: 1542 AN: 152114 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.00239

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00314

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000830

Gnomad FIN AF: 0.0365

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0145

Gnomad OTH AF: 0.00525

GnomAD2 exomes AF: 0.0105 AC: 2595 AN: 247030 AF XY: 0.0100

Gnomad AFR exome AF: 0.00215

Gnomad AMR exome AF: 0.00200

Gnomad ASJ exome AF: 0.000800

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0342

Gnomad NFE exome AF: 0.0150

Gnomad OTH exome AF: 0.00701

GnomAD4 exome AF: 0.0123 AC: 17948 AN: 1459312 Hom.: 166 Cov.: 31 AF XY: 0.0119 AC XY: 8605 AN XY: 725996

African (AFR) AF: 0.00159 AC: 53 AN: 33292

American (AMR) AF: 0.00205 AC: 91 AN: 44342

Ashkenazi Jewish (ASJ) AF: 0.00127 AC: 33 AN: 26068

East Asian (EAS) AF: 0.00 AC: 0 AN: 39558

South Asian (SAS) AF: 0.000558 AC: 48 AN: 85968

European-Finnish (FIN) AF: 0.0335 AC: 1787 AN: 53352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.0138 AC: 15373 AN: 1110704

Other (OTH) AF: 0.00934 AC: 563 AN: 60272

GnomAD4 genome AF: 0.0101 AC: 1541 AN: 152232 Hom.: 12 Cov.: 32 AF XY: 0.0106 AC XY: 789 AN XY: 74424

African (AFR) AF: 0.00238 AC: 99 AN: 41558

American (AMR) AF: 0.00314 AC: 48 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5172

South Asian (SAS) AF: 0.000831 AC: 4 AN: 4816

European-Finnish (FIN) AF: 0.0365 AC: 387 AN: 10594

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

European-Non Finnish (NFE) AF: 0.0145 AC: 987 AN: 68016

Other (OTH) AF: 0.00520 AC: 11 AN: 2116

Alfa AF: 0.0120 Hom.: 13

Bravo AF: 0.00698

Asia WGS AF: 0.00115 AC: 4 AN: 3476

EpiCase AF: 0.00972

EpiControl AF: 0.0112

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	7.0
DANN	Benign	0.62
PhyloP100		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs117638434; hg19: chr15-36989578; COSMIC: COSV57712674; COSMIC: COSV57712674;