rs374465951

Variant names:

• chr16-4513848-C-A
• rs374465951
• NM_013399.3:c.89G>T

Your query was ambiguous. Multiple possible variants found:

• chr16-4513848-C-A
• chr16-4513848-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_013399.3(CDIP1):​c.89G>T​(p.Arg30Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000706 in 1,416,506 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R30H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: CDIP1 NM_013399.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.338

Genes affected

CDIP1 (HGNC:13234): (cell death inducing p53 target 1) Predicted to enable metal ion binding activity. Acts upstream of or within intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator and tumor necrosis factor-mediated signaling pathway. Located in cytoplasmic side of late endosome membrane; cytoplasmic side of lysosomal membrane; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.045050412).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDIP1	NM_013399.3	c.89G>T	p.Arg30Leu	missense_variant	Exon 4 of 6	ENST00000567695.6	NP_037531.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDIP1	ENST00000567695.6	c.89G>T	p.Arg30Leu	missense_variant	Exon 4 of 6	1	NM_013399.3	ENSP00000457877.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.06e-7 AC: 1 AN: 1416506 Hom.: 0 Cov.: 31 AF XY: 0.00000143 AC XY: 1 AN XY: 701272

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.17e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.018	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	16
DANN	Benign	0.80
DEOGEN2	Benign	0.013	T;T;T;.;.;.;.;.
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.37
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.73	.;.;T;T;T;T;T;T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.045	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.0	L;L;L;L;L;.;.;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.72	N;N;N;N;N;.;.;.
REVEL	Benign	0.11
Sift	Benign	0.086	T;T;T;T;T;.;.;.
Sift4G	Benign	0.17	T;T;T;T;T;T;.;T
Polyphen		0.0040	B;B;B;.;.;.;.;.
Vest4		0.32
MutPred		0.27		Loss of methylation at R30 (P = 0.0278);Loss of methylation at R30 (P = 0.0278);Loss of methylation at R30 (P = 0.0278);Loss of methylation at R30 (P = 0.0278);Loss of methylation at R30 (P = 0.0278);Loss of methylation at R30 (P = 0.0278);Loss of methylation at R30 (P = 0.0278);Loss of methylation at R30 (P = 0.0278);
MVP		0.28
MPC		0.24
ClinPred		0.17	T
GERP RS		3.5
Varity_R		0.17
gMVP		0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs374465951; hg19: chr16-4563849;