Genetic Variant CACFD1:c.*1135T>C (chr9-133469788-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.851

Publications

16 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CACFD1	NM_017586.5	MANE Select	c.*1135T>C	3_prime_UTR	Exon 5 of 5	NP_060056.1
CACFD1	NM_001242369.2		c.*1077T>C	3_prime_UTR	Exon 6 of 6	NP_001229298.1
CACFD1	NM_001242370.2		c.*1077T>C	3_prime_UTR	Exon 5 of 5	NP_001229299.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CACFD1	ENST00000316948.9	TSL:1 MANE Select	c.*1135T>C	3_prime_UTR	Exon 5 of 5	ENSP00000317121.4
CACFD1	ENST00000540581.5	TSL:2	c.*1077T>C	3_prime_UTR	Exon 6 of 6	ENSP00000440832.1
CACFD1	ENST00000542192.5	TSL:2	c.*1077T>C	3_prime_UTR	Exon 5 of 5	ENSP00000444328.1

Frequencies

GnomAD3 genomes

AF:

0.799

AC:

121534

AN:

152160

Hom.:

49142

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.841

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.880

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.799

AC:

121641

AN:

152278

Hom.:

49191

Cov.:

AF XY:

0.802

AC XY:

59706

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.673

AC:

27958

AN:

41542

American (AMR)

AF:

0.850

AC:

13009

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.737

AC:

2560

AN:

3472

East Asian (EAS)

AF:

0.917

AC:

4746

AN:

5178

South Asian (SAS)

AF:

0.874

AC:

4221

AN:

4832

European-Finnish (FIN)

AF:

0.828

AC:

8786

AN:

10608

Middle Eastern (MID)

AF:

0.820

AC:

241

AN:

294

European-Non Finnish (NFE)

AF:

0.851

AC:

57851

AN:

68018

Other (OTH)

AF:

0.807

AC:

1707

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

1288

2576

3863

5151

6439

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

870

1740

2610

3480

4350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.823

Hom.:

11775

Bravo

AF:

0.792

Asia WGS

AF:

0.878

AC:

3052

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

2.7

(source)

DANN

Benign

0.72

PhyloP100

-0.85

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over