rs866256519

Variant names:

• chr9-133460110-C-A
• rs866256519
• NM_017586.5:c.44C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017586.5(CACFD1):​c.44C>A​(p.Ala15Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000819 in 1,562,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000089 (0 hom.)
• Consequence: CACFD1 NM_017586.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.187
• Publications: 0 publications found

Genes affected

CACFD1 (HGNC:1365): (calcium channel flower domain containing 1) Predicted to be involved in vesicle-mediated transport. Predicted to be integral component of membrane. [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=0.050433517).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017586.5. 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
	CACFD1	NM_017586.5	MANE Select	c.44C>A	p.Ala15Glu	missense	Exon 1 of 5	NP_060056.1	Q9UGQ2-1
	CACFD1	NM_001242369.2		c.44C>A	p.Ala15Glu	missense	Exon 1 of 6	NP_001229298.1	Q9UGQ2-4
	CACFD1	NM_001242370.2		c.44C>A	p.Ala15Glu	missense	Exon 1 of 5	NP_001229299.1	Q9UGQ2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACFD1	ENST00000316948.9	TSL:1 MANE Select	c.44C>A	p.Ala15Glu	missense	Exon 1 of 5	ENSP00000317121.4	Q9UGQ2-1
	CACFD1	ENST00000540581.5	TSL:2	c.44C>A	p.Ala15Glu	missense	Exon 1 of 6	ENSP00000440832.1	Q9UGQ2-4
	CACFD1	ENST00000542192.5	TSL:2	c.44C>A	p.Ala15Glu	missense	Exon 1 of 5	ENSP00000444328.1	Q9UGQ2-3

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152202 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000121 AC: 2 AN: 165466 AF XY: 0.0000112

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000317

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000886 AC: 125 AN: 1410576 Hom.: 0 Cov.: 32 AF XY: 0.0000946 AC XY: 66 AN XY: 697638

African (AFR) AF: 0.00 AC: 0 AN: 31752

American (AMR) AF: 0.00 AC: 0 AN: 38808

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25344

East Asian (EAS) AF: 0.00 AC: 0 AN: 36492

South Asian (SAS) AF: 0.00 AC: 0 AN: 80844

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5480

European-Non Finnish (NFE) AF: 0.000105 AC: 114 AN: 1085210

Other (OTH) AF: 0.000189 AC: 11 AN: 58294

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152202 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74364

African (AFR) AF: 0.00 AC: 0 AN: 41456

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000117 Hom.: 0

Bravo AF: 0.0000189

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.061	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.083	D
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.19
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.26	N
REVEL	Benign	0.016
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.14	T
Polyphen		0.0010	B
Vest4		0.25
MutPred		0.20		Gain of solvent accessibility (P = 0.0068)
MVP		0.067
MPC		0.14
ClinPred		0.20	T
GERP RS		2.4
PromoterAI		0.028	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Varity_R		0.060
gMVP		0.79
Mutation Taster		=81/19	polymorphism

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: rs866256519; hg19: chr9-136325232;