chr11-72841540-G-A
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_014824.3(FCHSD2):c.1970C>T(p.Pro657Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000932 in 1,611,086 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0050 ( 10 hom., cov: 32)
Exomes 𝑓: 0.00050 ( 8 hom. )
Consequence
FCHSD2
NM_014824.3 missense
NM_014824.3 missense
Scores
4
4
8
Clinical Significance
Conservation
PhyloP100: 9.04
Genes affected
FCHSD2 (HGNC:29114): (FCH and double SH3 domains 2) Enables phosphatidylinositol-3,4,5-trisphosphate binding activity and phosphatidylinositol-3,4-bisphosphate binding activity. Involved in clathrin-dependent endocytosis and positive regulation of Arp2/3 complex-mediated actin nucleation. Located in plasma membrane. Colocalizes with clathrin-coated pit. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.007178694).
BP6
?
Variant 11-72841540-G-A is Benign according to our data. Variant chr11-72841540-G-A is described in ClinVar as [Benign]. Clinvar id is 787382.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00504 (766/152084) while in subpopulation AFR AF= 0.0177 (732/41470). AF 95% confidence interval is 0.0166. There are 10 homozygotes in gnomad4. There are 366 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 763 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FCHSD2 | NM_014824.3 | c.1970C>T | p.Pro657Leu | missense_variant | 18/20 | ENST00000409418.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FCHSD2 | ENST00000409418.9 | c.1970C>T | p.Pro657Leu | missense_variant | 18/20 | 2 | NM_014824.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00502 AC: 763AN: 151966Hom.: 10 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00140 AC: 343AN: 245682Hom.: 4 AF XY: 0.00108 AC XY: 144AN XY: 132752
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GnomAD4 exome AF: 0.000504 AC: 736AN: 1459002Hom.: 8 Cov.: 33 AF XY: 0.000425 AC XY: 308AN XY: 725528
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GnomAD4 genome ? AF: 0.00504 AC: 766AN: 152084Hom.: 10 Cov.: 32 AF XY: 0.00492 AC XY: 366AN XY: 74340
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210
Asia WGS
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3478
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jul 23, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Pathogenic
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D;D;D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;D;N
REVEL
Benign
Sift
Uncertain
D;D;D;D;D
Sift4G
Pathogenic
D;D;D;D;D
Polyphen
1.0, 0.086
.;.;D;.;B
Vest4
MVP
MPC
0.89
ClinPred
T
GERP RS
Varity_R
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