rs11552068

chr21-44330285-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_004928.3(CFAP410):c.684T>C(p.Asp228=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00915 in 1,609,542 control chromosomes in the GnomAD database, including 711 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.038 (335 hom., cov: 34)
  • Exomes 𝑓: 0.0061 (376 hom.)
• Consequence: CFAP410 NM_004928.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.228

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 21-44330285-A-G is Benign according to our data. Variant chr21-44330285-A-G is described in ClinVar as [Benign]. Clinvar id is 259588.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.228 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFAP410	NM_004928.3	c.684T>C	p.Asp228=	synonymous_variant	7/7	ENST00000339818.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFAP410	ENST00000339818.9	c.684T>C	p.Asp228=	synonymous_variant	7/7	1	NM_004928.3	P4

Frequencies

GnomAD3 genomes AF: 0.0382 AC: 5809 AN: 152174 Hom.: 332 Cov.: 34

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0303

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0293

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00490

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000559

Gnomad OTH AF: 0.0349

GnomAD3 exomes AF: 0.0182 AC: 4276 AN: 234990 Hom.: 179 AF XY: 0.0139 AC XY: 1797 AN XY: 128906

Gnomad AFR exome AF: 0.127

Gnomad AMR exome AF: 0.0492

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0284

Gnomad SAS exome AF: 0.00107

Gnomad FIN exome AF: 0.00429

Gnomad NFE exome AF: 0.000512

Gnomad OTH exome AF: 0.0101

GnomAD4 exome AF: 0.00609 AC: 8880 AN: 1457250 Hom.: 376 Cov.: 31 AF XY: 0.00538 AC XY: 3897 AN XY: 724720

Gnomad4 AFR exome AF: 0.128

Gnomad4 AMR exome AF: 0.0479

Gnomad4 ASJ exome AF: 0.0000384

Gnomad4 EAS exome AF: 0.0229

Gnomad4 SAS exome AF: 0.00117

Gnomad4 FIN exome AF: 0.00455

Gnomad4 NFE exome AF: 0.000248

Gnomad4 OTH exome AF: 0.0143

GnomAD4 genome AF: 0.0384 AC: 5841 AN: 152292 Hom.: 335 Cov.: 34 AF XY: 0.0377 AC XY: 2806 AN XY: 74480

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.0306

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0293

Gnomad4 SAS AF: 0.00186

Gnomad4 FIN AF: 0.00490

Gnomad4 NFE AF: 0.000544

Gnomad4 OTH AF: 0.0355

Alfa AF: 0.0108 Hom.: 29

Bravo AF: 0.0445

Asia WGS AF: 0.0280 AC: 98 AN: 3478

EpiCase AF: 0.000654

EpiControl AF: 0.000238

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	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

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
BayesDel_noAF	Benign	-0.93
Cadd	Benign	3.6
Dann	Benign	0.68
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

Other links and lift over

dbSNP: rs11552068; hg19: chr21-45750168;