Variant 9-133463535-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_017586.5(CACFD1):c.174T>G(p.Ile58Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00672 in 1,613,976 control chromosomes in the GnomAD database, including 49 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0053 ( 6 hom., cov: 34)

Exomes 𝑓: 0.0069 ( 43 hom. )

Consequence

CACFD1
NM_017586.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.29

Variant links:

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 links:

CACFD1 (HGNC:):

CACFD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.056706637).

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACFD1	NM_017586.5 linkuse as main transcript	c.174T>G	p.Ile58Met	missense_variant	2/5	ENST00000316948.9	NP_060056.1	Q9UGQ2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACFD1	ENST00000316948.9 linkuse as main transcript	c.174T>G	p.Ile58Met	missense_variant	2/5	1	NM_017586.5	ENSP00000317121.4		Q9UGQ2-1

Frequencies

GnomAD3 genomes

AF:

0.00529

AC:

805

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.00330

Gnomad AMR

AF:

0.00334

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00744

Gnomad FIN

AF:

0.0145

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.00709

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00601

AC:

1511

AN:

251380

Hom.:

AF XY:

0.00633

AC XY:

860

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.00188

Gnomad ASJ exome

AF:

0.00298

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00866

Gnomad FIN exome

AF:

0.0139

Gnomad NFE exome

AF:

0.00697

Gnomad OTH exome

AF:

0.00603

GnomAD4 exome

AF:

0.00686

AC:

10032

AN:

1461710

Hom.:

Cov.:

AF XY:

0.00698

AC XY:

5072

AN XY:

727152

show subpopulations

Gnomad4 AFR exome

AF:

0.00117

Gnomad4 AMR exome

AF:

0.00190

Gnomad4 ASJ exome

AF:

0.00275

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00874

Gnomad4 FIN exome

AF:

0.0129

Gnomad4 NFE exome

AF:

0.00716

Gnomad4 OTH exome

AF:

0.00667

GnomAD4 genome

AF:

0.00529

AC:

806

AN:

152266

Hom.:

Cov.:

AF XY:

0.00579

AC XY:

431

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00116

Gnomad4 AMR

AF:

0.00333

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00786

Gnomad4 FIN

AF:

0.0145

Gnomad4 NFE

AF:

0.00709

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00839

Hom.:

18457

TwinsUK

AF:

0.00917

AC:

ALSPAC

AF:

0.00701

AC:

ExAC

AF:

0.00593

AC:

720

EpiCase

AF:

0.00627

EpiControl

AF:

0.00652

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.019

BayesDel_noAF

Pathogenic

0.21

CADD

Benign

7.4

DANN

Uncertain

0.99

DEOGEN2

Benign

0.075

.;.;.;T;.

Eigen

Benign

-0.89

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.15

LIST_S2

Uncertain

0.88

D;D;D;D;D

MetaRNN

Benign

0.057

T;T;T;T;T

MetaSVM

Uncertain

0.25

MutationAssessor

Uncertain

2.1

M;M;M;M;.

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.4

N;N;N;N;N

REVEL

Uncertain

0.40

Sift

Benign

0.092

T;T;D;D;D

Sift4G

Benign

0.31

T;T;T;T;T

Polyphen

1.0, 0.52

.;.;D;P;.

Vest4

0.81

MVP

0.29

MPC

0.56

ClinPred

0.051

GERP RS

-2.6

Varity_R

0.12

gMVP

0.86

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over