21-44330063-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004928.3(CFAP410):c.*135G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00564 in 1,039,768 control chromosomes in the GnomAD database, including 233 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.024 (158 hom., cov: 33)
  • Exomes 𝑓: 0.0026 (75 hom.)
• Consequence: CFAP410 NM_004928.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.48

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 21-44330063-C-T is Benign according to our data. Variant chr21-44330063-C-T is described in ClinVar as [Benign]. Clinvar id is 1233826.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFAP410	NM_004928.3	c.*135G>A		3_prime_UTR_variant	7/7	ENST00000339818.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFAP410	ENST00000339818.9	c.*135G>A		3_prime_UTR_variant	7/7	1	NM_004928.3	P4
	ENST00000444409.1	n.142+17G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0236 AC: 3586 AN: 152228 Hom.: 157 Cov.: 33

Gnomad AFR AF: 0.0822

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00824

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.0134

GnomAD4 exome AF: 0.00256 AC: 2269 AN: 887422 Hom.: 75 Cov.: 12 AF XY: 0.00218 AC XY: 969 AN XY: 444442

Gnomad4 AFR exome AF: 0.0792

Gnomad4 AMR exome AF: 0.00534

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000607

Gnomad4 SAS exome AF: 0.000941

Gnomad4 FIN exome AF: 0.0000657

Gnomad4 NFE exome AF: 0.000153

Gnomad4 OTH exome AF: 0.00538

GnomAD4 genome AF: 0.0236 AC: 3595 AN: 152346 Hom.: 158 Cov.: 33 AF XY: 0.0228 AC XY: 1698 AN XY: 74510

Gnomad4 AFR AF: 0.0822

Gnomad4 AMR AF: 0.00823

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.0133

Alfa AF: 0.00324 Hom.: 4

Bravo AF: 0.0270

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 11, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.74
Dann	Benign	0.68

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: rs115529052; hg19: chr21-45749946;