9-133463535-T-C

Position:

• chr9-133463535-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

CACFD1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACFD1	NM_017586.5	c.174T>C	p.Ile58Ile	synonymous_variant	2/5	ENST00000316948.9	NP_060056.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACFD1	ENST00000316948.9	c.174T>C	p.Ile58Ile	synonymous_variant	2/5	1	NM_017586.5	ENSP00000317121.4

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

GnomAD3 exomes AF: 0.838 AC: 210720 AN: 251380 Hom.: 88690 AF XY: 0.838 AC XY: 113849 AN XY: 135870

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 SAS exome AF: 0.860

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

Gnomad4 AFR exome AF: 0.692

Gnomad4 AMR exome AF: 0.865

Gnomad4 ASJ exome AF: 0.749

Gnomad4 EAS exome AF: 0.911

Gnomad4 SAS exome AF: 0.860

Gnomad4 FIN exome AF: 0.834

Gnomad4 NFE exome AF: 0.853

Gnomad4 OTH exome AF: 0.842

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

Gnomad4 AFR AF: 0.699

Gnomad4 AMR AF: 0.853

Gnomad4 ASJ AF: 0.737

Gnomad4 EAS AF: 0.929

Gnomad4 SAS AF: 0.866

Gnomad4 FIN AF: 0.814

Gnomad4 NFE AF: 0.845

Gnomad4 OTH AF: 0.808

Alfa AF: 0.821 Hom.: 18457

Bravo AF: 0.802

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	1.9
DANN	Benign	0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs3124765; hg19: chr9-136328657;