9-133463535-T-C

Variant names:

• chr9-133463535-T-C
• rs3124765
• NM_017586.5:c.174T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_017586.5(CACFD1):​c.174T>C​(p.Ile58Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.844 in 1,613,800 control chromosomes in the GnomAD database, including 576,497 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.80 (49487 hom., cov: 34)
  • Exomes 𝑓: 0.85 (527010 hom.)
• Consequence: CACFD1 NM_017586.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.29
• Publications: 37 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP7: Synonymous conserved (PhyloP=-2.29 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.907 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACFD1	NM_017586.5	MANE Select	c.174T>C	p.Ile58Ile	synonymous	Exon 2 of 5	NP_060056.1
	CACFD1	NM_001242369.2		c.174T>C	p.Ile58Ile	synonymous	Exon 2 of 6	NP_001229298.1
	CACFD1	NM_001242370.2		c.174T>C	p.Ile58Ile	synonymous	Exon 2 of 5	NP_001229299.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACFD1	ENST00000316948.9	TSL:1 MANE Select	c.174T>C	p.Ile58Ile	synonymous	Exon 2 of 5	ENSP00000317121.4
	CACFD1	ENST00000540581.5	TSL:2	c.174T>C	p.Ile58Ile	synonymous	Exon 2 of 6	ENSP00000440832.1
	CACFD1	ENST00000542192.5	TSL:2	c.174T>C	p.Ile58Ile	synonymous	Exon 2 of 5	ENSP00000444328.1

Frequencies

GnomAD3 genomes AF: 0.803 AC: 122104 AN: 152108 Hom.: 49437 Cov.: 34

Gnomad AFR AF: 0.699

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.853

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.929

Gnomad SAS AF: 0.865

Gnomad FIN AF: 0.814

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.845

Gnomad OTH AF: 0.806

GnomAD2 exomes AF: 0.838 AC: 210720 AN: 251380 AF XY: 0.838

Gnomad AFR exome AF: 0.698

Gnomad AMR exome AF: 0.868

Gnomad ASJ exome AF: 0.745

Gnomad EAS exome AF: 0.933

Gnomad FIN exome AF: 0.825

Gnomad NFE exome AF: 0.839

Gnomad OTH exome AF: 0.833

GnomAD4 exome AF: 0.848 AC: 1239849 AN: 1461574 Hom.: 527010 Cov.: 49 AF XY: 0.848 AC XY: 616572 AN XY: 727080

African (AFR) AF: 0.692 AC: 23168 AN: 33472

American (AMR) AF: 0.865 AC: 38672 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.749 AC: 19576 AN: 26132

East Asian (EAS) AF: 0.911 AC: 36177 AN: 39698

South Asian (SAS) AF: 0.860 AC: 74150 AN: 86256

European-Finnish (FIN) AF: 0.834 AC: 44442 AN: 53286

Middle Eastern (MID) AF: 0.808 AC: 4660 AN: 5766

European-Non Finnish (NFE) AF: 0.853 AC: 948135 AN: 1111858

Other (OTH) AF: 0.842 AC: 50869 AN: 60386

GnomAD4 genome AF: 0.803 AC: 122215 AN: 152226 Hom.: 49487 Cov.: 34 AF XY: 0.805 AC XY: 59923 AN XY: 74436

African (AFR) AF: 0.699 AC: 29026 AN: 41506

American (AMR) AF: 0.853 AC: 13043 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.737 AC: 2556 AN: 3468

East Asian (EAS) AF: 0.929 AC: 4815 AN: 5182

South Asian (SAS) AF: 0.866 AC: 4184 AN: 4832

European-Finnish (FIN) AF: 0.814 AC: 8631 AN: 10608

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.845 AC: 57464 AN: 68022

Other (OTH) AF: 0.808 AC: 1706 AN: 2112

Alfa AF: 0.719 Hom.: 33083

Bravo AF: 0.802

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	1.9
DANN	Benign	0.60
PhyloP100		-2.3
Mutation Taster		=100/0	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: rs3124765; hg19: chr9-136328657; COSMIC: COSV99390351; COSMIC: COSV99390351;