chr15-36691761-T-C

Variant names:

• chr15-36691761-T-C
• rs7183415
• NM_001321759.2:c.423T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001321759.2(CDIN1):​c.423T>C​(p.Tyr141Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,587,854 control chromosomes in the GnomAD database, including 11,535 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1134 hom., cov: 30)
  • Exomes 𝑓: 0.11 (10401 hom.)
• Consequence: CDIN1 NM_001321759.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 2.42
• Publications: 14 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 15-36691761-T-C is Benign according to our data. Variant chr15-36691761-T-C is described in ClinVar as Benign. ClinVar VariationId is 257533.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.42 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.365 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.423T>C	p.Tyr141Tyr	synonymous	Exon 6 of 11	NP_001308688.1	Q9Y2V0-1
	CDIN1	NM_001321761.2		c.423T>C	p.Tyr141Tyr	synonymous	Exon 6 of 11	NP_001308690.1	H3BS01
	CDIN1	NM_001290233.2		c.423T>C	p.Tyr141Tyr	synonymous	Exon 6 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.423T>C	p.Tyr141Tyr	synonymous	Exon 6 of 11	ENSP00000455397.1	Q9Y2V0-1
	CDIN1	ENST00000437989.6	TSL:1	c.423T>C	p.Tyr141Tyr	synonymous	Exon 6 of 12	ENSP00000401362.2	Q9Y2V0-1
	CDIN1	ENST00000562877.5	TSL:1	c.129T>C	p.Tyr43Tyr	synonymous	Exon 6 of 11	ENSP00000457854.1	Q9Y2V0-2

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16156 AN: 151974 Hom.: 1133 Cov.: 30

Gnomad AFR AF: 0.0993

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.0874

Gnomad ASJ AF: 0.0744

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.0688

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0957

Gnomad OTH AF: 0.0881

GnomAD2 exomes AF: 0.122 AC: 27222 AN: 223028 AF XY: 0.124

Gnomad AFR exome AF: 0.108

Gnomad AMR exome AF: 0.0778

Gnomad ASJ exome AF: 0.0743

Gnomad EAS exome AF: 0.377

Gnomad FIN exome AF: 0.0712

Gnomad NFE exome AF: 0.0929

Gnomad OTH exome AF: 0.102

GnomAD4 exome AF: 0.107 AC: 153381 AN: 1435764 Hom.: 10401 Cov.: 29 AF XY: 0.109 AC XY: 77355 AN XY: 712904

African (AFR) AF: 0.108 AC: 3582 AN: 33050

American (AMR) AF: 0.0783 AC: 3341 AN: 42678

Ashkenazi Jewish (ASJ) AF: 0.0739 AC: 1903 AN: 25762

East Asian (EAS) AF: 0.367 AC: 14368 AN: 39158

South Asian (SAS) AF: 0.188 AC: 15546 AN: 82904

European-Finnish (FIN) AF: 0.0728 AC: 3825 AN: 52544

Middle Eastern (MID) AF: 0.0716 AC: 410 AN: 5730

European-Non Finnish (NFE) AF: 0.0947 AC: 103633 AN: 1094442

Other (OTH) AF: 0.114 AC: 6773 AN: 59496

GnomAD4 genome AF: 0.106 AC: 16171 AN: 152090 Hom.: 1134 Cov.: 30 AF XY: 0.108 AC XY: 8040 AN XY: 74322

African (AFR) AF: 0.0995 AC: 4132 AN: 41508

American (AMR) AF: 0.0874 AC: 1335 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0744 AC: 258 AN: 3466

East Asian (EAS) AF: 0.379 AC: 1939 AN: 5120

South Asian (SAS) AF: 0.205 AC: 989 AN: 4816

European-Finnish (FIN) AF: 0.0688 AC: 729 AN: 10590

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0957 AC: 6504 AN: 67996

Other (OTH) AF: 0.0886 AC: 187 AN: 2110

Alfa AF: 0.0973 Hom.: 2045

Bravo AF: 0.105

Asia WGS AF: 0.248 AC: 862 AN: 3478

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	-0.54
CADD	Benign	9.7
DANN	Benign	0.51
PhyloP100		2.4
Mutation Taster		=82/18	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: rs7183415; hg19: chr15-36983962; COSMIC: COSV57715598; COSMIC: COSV57715598;