rs11552066

chr21-44330262-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004928.3(CFAP410):c.707A>G(p.Gln236Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,602,162 control chromosomes in the GnomAD database, including 9,802 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q236W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.093 (742 hom., cov: 34)
  • Exomes 𝑓: 0.11 (9060 hom.)
• Consequence: CFAP410 NM_004928.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 3.07

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0013685822).
• BP6: Variant 21-44330262-T-C is Benign according to our data. Variant chr21-44330262-T-C is described in ClinVar as [Benign]. Clinvar id is 259589.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFAP410	NM_004928.3	c.707A>G	p.Gln236Arg	missense_variant	7/7	ENST00000339818.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFAP410	ENST00000339818.9	c.707A>G	p.Gln236Arg	missense_variant	7/7	1	NM_004928.3	P4
	ENST00000444409.1			upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.0934 AC: 14212 AN: 152212 Hom.: 743 Cov.: 34

Gnomad AFR AF: 0.0505

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.0908

Gnomad EAS AF: 0.0246

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.113

GnomAD3 exomes AF: 0.105 AC: 23288 AN: 220876 Hom.: 1317 AF XY: 0.107 AC XY: 12972 AN XY: 121372

Gnomad AFR exome AF: 0.0471

Gnomad AMR exome AF: 0.151

Gnomad ASJ exome AF: 0.0839

Gnomad EAS exome AF: 0.0238

Gnomad SAS exome AF: 0.110

Gnomad FIN exome AF: 0.107

Gnomad NFE exome AF: 0.113

Gnomad OTH exome AF: 0.109

GnomAD4 exome AF: 0.109 AC: 158192 AN: 1449832 Hom.: 9060 Cov.: 31 AF XY: 0.109 AC XY: 78808 AN XY: 720382

Gnomad4 AFR exome AF: 0.0447

Gnomad4 AMR exome AF: 0.153

Gnomad4 ASJ exome AF: 0.0862

Gnomad4 EAS exome AF: 0.0232

Gnomad4 SAS exome AF: 0.110

Gnomad4 FIN exome AF: 0.109

Gnomad4 NFE exome AF: 0.113

Gnomad4 OTH exome AF: 0.102

GnomAD4 genome AF: 0.0933 AC: 14212 AN: 152330 Hom.: 742 Cov.: 34 AF XY: 0.0936 AC XY: 6974 AN XY: 74492

Gnomad4 AFR AF: 0.0504

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.0908

Gnomad4 EAS AF: 0.0249

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.111

Alfa AF: 0.110 Hom.: 391

Bravo AF: 0.0927

TwinsUK AF: 0.107 AC: 397

ALSPAC AF: 0.118 AC: 456

ESP6500AA AF: 0.0440 AC: 192

ESP6500EA AF: 0.110 AC: 939

ExAC AF: 0.0967 AC: 11627

Asia WGS AF: 0.0780 AC: 269 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 30, 2021	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.66
Cadd	Benign	9.1
Dann	Benign	0.87
DEOGEN2	Benign	0.012	T;.;.
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.81
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.64	T;T;T
MetaRNN	Benign	0.0014	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P;P;P
PROVEAN	Benign	-1.6	N;N;N
REVEL	Benign	0.064
Sift	Benign	0.30	T;T;T
Sift4G	Benign	0.56	T;T;T
Polyphen		0.0030	B;.;.
Vest4		0.089
MPC		0.18
ClinPred		0.0037	T
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.063
gMVP		0.20

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

Other links and lift over

dbSNP: rs11552066; hg19: chr21-45750145; COSMIC: COSV57394551; COSMIC: COSV57394551;