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GeneBe

11-72868021-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_014824.3(FCHSD2):c.1152T>C(p.Ile384=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0016 in 1,556,024 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0078 ( 14 hom., cov: 32)
Exomes 𝑓: 0.00092 ( 14 hom. )

Consequence

FCHSD2
NM_014824.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.526
Variant links:
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 -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 11-72868021-A-G is Benign according to our data. Variant chr11-72868021-A-G is described in ClinVar as [Benign]. Clinvar id is 786201.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.526 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00783 (1192/152254) while in subpopulation AFR AF= 0.0268 (1115/41544). AF 95% confidence interval is 0.0255. There are 14 homozygotes in gnomad4. There are 546 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 1190 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FCHSD2NM_014824.3 linkuse as main transcriptc.1152T>C p.Ile384= synonymous_variant 13/20 ENST00000409418.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FCHSD2ENST00000409418.9 linkuse as main transcriptc.1152T>C p.Ile384= synonymous_variant 13/202 NM_014824.3 P1O94868-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00782
AC:
1190
AN:
152136
Hom.:
14
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0268
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00347
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00957
GnomAD3 exomes
AF:
0.00228
AC:
376
AN:
164964
Hom.:
1
AF XY:
0.00173
AC XY:
149
AN XY:
86032
show subpopulations
Gnomad AFR exome
AF:
0.0301
Gnomad AMR exome
AF:
0.00246
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000880
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000139
Gnomad OTH exome
AF:
0.00130
GnomAD4 exome
AF:
0.000920
AC:
1292
AN:
1403770
Hom.:
14
Cov.:
31
AF XY:
0.000813
AC XY:
563
AN XY:
692560
show subpopulations
Gnomad4 AFR exome
AF:
0.0309
Gnomad4 AMR exome
AF:
0.00245
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000139
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000407
Gnomad4 OTH exome
AF:
0.00240
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00783
AC:
1192
AN:
152254
Hom.:
14
Cov.:
32
AF XY:
0.00733
AC XY:
546
AN XY:
74452
show subpopulations
Gnomad4 AFR
AF:
0.0268
Gnomad4 AMR
AF:
0.00347
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00947
Alfa
AF:
0.00338
Hom.:
3
Bravo
AF:
0.00876
Asia WGS
AF:
0.00202
AC:
7
AN:
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 submitterclinical testingInvitaeDec 14, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.43
Cadd
Benign
10
Dann
Benign
0.73

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.

Other links and lift over

dbSNP: rs77605839; hg19: chr11-72579066; API