9-133469788-T-C

Position:

• chr9-133469788-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017586.5(CACFD1):​c.*1135T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.799 in 152,342 control chromosomes in the GnomAD database, including 49,215 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 (49191 hom., cov: 37)
  • Exomes 𝑓: 0.84 (24 hom.)
• Consequence: CACFD1 NM_017586.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.851

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACFD1	NM_017586.5	c.*1135T>C		3_prime_UTR_variant	5/5	ENST00000316948.9	NP_060056.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACFD1	ENST00000316948.9	c.*1135T>C		3_prime_UTR_variant	5/5	1	NM_017586.5	ENSP00000317121.4
CACFD1	ENST00000540581.5	c.*1077T>C		3_prime_UTR_variant	6/6	2		ENSP00000440832.1
CACFD1	ENST00000542192.5	c.*1077T>C		3_prime_UTR_variant	5/5	2		ENSP00000444328.1
CACFD1	ENST00000291722.11	c.*1135T>C		3_prime_UTR_variant	4/4	2		ENSP00000291722.7

Frequencies

GnomAD3 genomes AF: 0.799 AC: 121534 AN: 152160 Hom.: 49142 Cov.: 37

Gnomad AFR AF: 0.673

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.850

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.917

Gnomad SAS AF: 0.872

Gnomad FIN AF: 0.828

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.851

Gnomad OTH AF: 0.806

GnomAD4 exome AF: 0.844 AC: 54 AN: 64 Hom.: 24 Cov.: 0 AF XY: 0.841 AC XY: 37 AN XY: 44

Gnomad4 EAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.880

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.799 AC: 121641 AN: 152278 Hom.: 49191 Cov.: 37 AF XY: 0.802 AC XY: 59706 AN XY: 74460

Gnomad4 AFR AF: 0.673

Gnomad4 AMR AF: 0.850

Gnomad4 ASJ AF: 0.737

Gnomad4 EAS AF: 0.917

Gnomad4 SAS AF: 0.874

Gnomad4 FIN AF: 0.828

Gnomad4 NFE AF: 0.851

Gnomad4 OTH AF: 0.807

Alfa AF: 0.830 Hom.: 10386

Bravo AF: 0.792

Asia WGS AF: 0.878 AC: 3052 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.7
DANN	Benign	0.72

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: rs3094379; hg19: chr9-136334910;