rs139444685

Positions:

• chr15-36692111-C-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001321759.2(CDIN1):​c.427-15C>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00411 in 1,613,218 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0031 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0042 (14 hom.)
• Consequence: CDIN1 NM_001321759.2 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.48

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 15-36692111-C-G is Benign according to our data. Variant chr15-36692111-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 257534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDIN1	NM_001321759.2	c.427-15C>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000566621.6	NP_001308688.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDIN1	ENST00000566621.6	c.427-15C>G		splice_polypyrimidine_tract_variant, intron_variant		5	NM_001321759.2	ENSP00000455397	P1

Frequencies

GnomAD3 genomes AF: 0.00313 AC: 476 AN: 152116 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000821

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.000755

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00544

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00273 AC: 679 AN: 248568 Hom.: 2 AF XY: 0.00272 AC XY: 367 AN XY: 134886

Gnomad AFR exome AF: 0.000907

Gnomad AMR exome AF: 0.00250

Gnomad ASJ exome AF: 0.00468

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000884

Gnomad FIN exome AF: 0.000606

Gnomad NFE exome AF: 0.00420

Gnomad OTH exome AF: 0.00298

GnomAD4 exome AF: 0.00422 AC: 6161 AN: 1460984 Hom.: 14 Cov.: 31 AF XY: 0.00415 AC XY: 3016 AN XY: 726778

Gnomad4 AFR exome AF: 0.000598

Gnomad4 AMR exome AF: 0.00289

Gnomad4 ASJ exome AF: 0.00563

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000835

Gnomad4 FIN exome AF: 0.000619

Gnomad4 NFE exome AF: 0.00498

Gnomad4 OTH exome AF: 0.00355

GnomAD4 genome AF: 0.00313 AC: 476 AN: 152234 Hom.: 0 Cov.: 31 AF XY: 0.00284 AC XY: 211 AN XY: 74426

Gnomad4 AFR AF: 0.000819

Gnomad4 AMR AF: 0.00229

Gnomad4 ASJ AF: 0.00403

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.000755

Gnomad4 NFE AF: 0.00544

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00501 Hom.: 0

Bravo AF: 0.00327

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	16
DANN	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs139444685; hg19: chr15-36984312;