16-4513848-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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. 17/22 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
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013399.3. 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
	CDIP1	NM_013399.3	MANE Select	c.89G>T	p.Arg30Leu	missense	Exon 4 of 6	NP_037531.2	Q9H305-1
	CDIP1	NM_001199054.2		c.89G>T	p.Arg30Leu	missense	Exon 4 of 6	NP_001185983.1	Q9H305-1
	CDIP1	NM_001199055.2		c.89G>T	p.Arg30Leu	missense	Exon 4 of 6	NP_001185984.1	Q9H305-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDIP1	ENST00000567695.6	TSL:1 MANE Select	c.89G>T	p.Arg30Leu	missense	Exon 4 of 6	ENSP00000457877.1	Q9H305-1
	CDIP1	ENST00000399599.7	TSL:1	c.89G>T	p.Arg30Leu	missense	Exon 3 of 5	ENSP00000382508.2	Q9H305-1
	CDIP1	ENST00000563332.6	TSL:1	c.89G>T	p.Arg30Leu	missense	Exon 4 of 6	ENSP00000454994.1	Q9H305-1

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32038

American (AMR) AF: 0.00 AC: 0 AN: 38138

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22608

East Asian (EAS) AF: 0.00 AC: 0 AN: 38948

South Asian (SAS) AF: 0.00 AC: 0 AN: 78912

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51128

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5514

European-Non Finnish (NFE) AF: 9.17e-7 AC: 1 AN: 1090738

Other (OTH) AF: 0.00 AC: 0 AN: 58482

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.37
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.34
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.72	N
REVEL	Benign	0.11
Sift	Benign	0.086	T
Sift4G	Benign	0.17	T
Polyphen		0.0040	B
Vest4		0.32
MutPred		0.27		Loss of methylation at R30 (P = 0.0278)
MVP		0.28
MPC		0.24
ClinPred		0.17	T
GERP RS		3.5
PromoterAI		-0.0018	Neutral
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

Other links and lift over

dbSNP: rs374465951; hg19: chr16-4563849;