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GeneBe

rs11870

chr21-44339162-C-Tchr21-44339162-C-G

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_004928.3(CFAP410):c.33G>A(p.Arg11=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 1,470,992 control chromosomes in the GnomAD database, including 42,087 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. R11R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.28 ( 6648 hom., cov: 31)
Exomes 𝑓: 0.22 ( 35439 hom. )

Consequence

CFAP410
NM_004928.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0680
Variant links:
Genes affected
CFAP410 (HGNC:1260): (cilia and flagella associated protein 410) Four alternatively spliced transcript variants encoding four different isoforms have been found for this nuclear gene. All isoforms contain leucine-rich repeats. Three of these isoforms are mitochondrial proteins and one of them lacks the target peptide, so is not located in mitochondrion. This gene is down-regulated in Down syndrome (DS) brain, which may represent mitochondrial dysfunction in DS patients. [provided by RefSeq, Sep 2012]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 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=-0.3).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 21-44339162-C-T is Benign according to our data. Variant chr21-44339162-C-T is described in ClinVar as [Benign]. Clinvar id is 259586.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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=0.068 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CFAP410NM_004928.3 linkuse as main transcriptc.33G>A p.Arg11= synonymous_variant 1/7 ENST00000339818.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CFAP410ENST00000339818.9 linkuse as main transcriptc.33G>A p.Arg11= synonymous_variant 1/71 NM_004928.3 P4O43822-1
CFAP410ENST00000397956.7 linkuse as main transcriptc.33G>A p.Arg11= synonymous_variant 1/71 O43822-4
CFAP410ENST00000325223.7 linkuse as main transcriptc.33G>A p.Arg11= synonymous_variant 1/71 A1O43822-3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.278
AC:
42128
AN:
151348
Hom.:
6642
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.425
Gnomad AMI
AF:
0.173
Gnomad AMR
AF:
0.257
Gnomad ASJ
AF:
0.186
Gnomad EAS
AF:
0.148
Gnomad SAS
AF:
0.378
Gnomad FIN
AF:
0.184
Gnomad MID
AF:
0.293
Gnomad NFE
AF:
0.217
Gnomad OTH
AF:
0.278
GnomAD3 exomes
AF:
0.240
AC:
21903
AN:
91162
Hom.:
2991
AF XY:
0.247
AC XY:
12666
AN XY:
51190
show subpopulations
Gnomad AFR exome
AF:
0.409
Gnomad AMR exome
AF:
0.250
Gnomad ASJ exome
AF:
0.182
Gnomad EAS exome
AF:
0.130
Gnomad SAS exome
AF:
0.354
Gnomad FIN exome
AF:
0.192
Gnomad NFE exome
AF:
0.210
Gnomad OTH exome
AF:
0.232
GnomAD4 exome
AF:
0.225
AC:
296327
AN:
1319536
Hom.:
35439
Cov.:
32
AF XY:
0.228
AC XY:
148263
AN XY:
650630
show subpopulations
Gnomad4 AFR exome
AF:
0.432
Gnomad4 AMR exome
AF:
0.262
Gnomad4 ASJ exome
AF:
0.182
Gnomad4 EAS exome
AF:
0.158
Gnomad4 SAS exome
AF:
0.356
Gnomad4 FIN exome
AF:
0.197
Gnomad4 NFE exome
AF:
0.213
Gnomad4 OTH exome
AF:
0.233
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.278
AC:
42175
AN:
151456
Hom.:
6648
Cov.:
31
AF XY:
0.277
AC XY:
20494
AN XY:
74026
show subpopulations
Gnomad4 AFR
AF:
0.425
Gnomad4 AMR
AF:
0.257
Gnomad4 ASJ
AF:
0.186
Gnomad4 EAS
AF:
0.149
Gnomad4 SAS
AF:
0.377
Gnomad4 FIN
AF:
0.184
Gnomad4 NFE
AF:
0.217
Gnomad4 OTH
AF:
0.278
Alfa
AF:
0.135
Hom.:
224
Bravo
AF:
0.288
Asia WGS
AF:
0.295
AC:
1012
AN:
3438

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingInvitaeJan 31, 2024- -
Benign, criteria provided, single submitterclinical testingGeneDxMay 04, 2021- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.30
Cadd
Benign
12
Dann
Benign
0.96
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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: rs11870; hg19: chr21-45759045; COSMIC: COSV57394557; COSMIC: COSV57394557; API