22-37297648-A-C
Variant names:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_013385.5(CYTH4):c.319A>C(p.Asn107His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00134 in 1,613,890 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0070 ( 11 hom., cov: 32)
Exomes 𝑓: 0.00074 ( 11 hom. )
Consequence
CYTH4
NM_013385.5 missense
NM_013385.5 missense
Scores
4
7
7
Clinical Significance
Conservation
PhyloP100: 9.31
Genes affected
CYTH4 (HGNC:9505): (cytohesin 4) This gene encodes a member of the PSCD family of proteins, which have an N-terminal coiled-coil motif, a central Sec7 domain, and a C-terminal pleckstrin homology (PH) domain. The coiled-coil motif is involved in homodimerization, the Sec7 domain contains guanine-nucleotide exchange protein (GEP) activity, and the PH domain interacts with phospholipids and is responsible for association of PSCDs with membranes. Members of this family function as GEPs for ADP-ribosylation factors (ARFs), which are guanine nucleotide-binding proteins involved in vesicular trafficking pathways. This protein exhibits GEP activity in vitro with ARF1 and ARF5, but is inactive with ARF6. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.01158908).
BP6
Variant 22-37297648-A-C is Benign according to our data. Variant chr22-37297648-A-C is described in ClinVar as [Benign]. Clinvar id is 734145.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00704 (1072/152320) while in subpopulation AFR AF= 0.0249 (1034/41564). AF 95% confidence interval is 0.0236. There are 11 homozygotes in gnomad4. There are 488 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 11 AR gene
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00703 AC: 1070AN: 152202Hom.: 11 Cov.: 32
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GnomAD3 exomes AF: 0.00178 AC: 448AN: 251480Hom.: 5 AF XY: 0.00111 AC XY: 151AN XY: 135916
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GnomAD4 exome AF: 0.000744 AC: 1088AN: 1461570Hom.: 11 Cov.: 30 AF XY: 0.000646 AC XY: 470AN XY: 727094
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GnomAD4 genome AF: 0.00704 AC: 1072AN: 152320Hom.: 11 Cov.: 32 AF XY: 0.00655 AC XY: 488AN XY: 74486
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided
- -
Jun 05, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Pathogenic
.;H;.;.
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
1.0
.;D;.;.
Vest4
0.71, 0.68, 0.68
MVP
MPC
1.2
ClinPred
T
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at