21-44330165-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.*33G>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 0.00393 in 1,542,758 control chromosomes in the GnomAD database, including 187 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.020 (101 hom., cov: 33)
  • Exomes 𝑓: 0.0022 (86 hom.)
• Consequence: CFAP410 NM_004928.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.99

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=-0.92).
• BP6: Variant 21-44330165-C-T is Benign according to our data. Variant chr21-44330165-C-T is described in ClinVar as [Benign]. Clinvar id is 1237703.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFAP410	NM_004928.3	c.*33G>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.*33G>A		3_prime_UTR_variant	7/7	1	NM_004928.3	P4
	ENST00000444409.1	n.57G>A		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes AF: 0.0196 AC: 2977 AN: 152246 Hom.: 100 Cov.: 33

Gnomad AFR AF: 0.0673

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00726

Gnomad ASJ AF: 0.00374

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000413

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000441

Gnomad OTH AF: 0.0139

GnomAD3 exomes AF: 0.00458 AC: 671 AN: 146444 Hom.: 15 AF XY: 0.00340 AC XY: 271 AN XY: 79736

Gnomad AFR exome AF: 0.0675

Gnomad AMR exome AF: 0.00330

Gnomad ASJ exome AF: 0.00325

Gnomad EAS exome AF: 0.0000886

Gnomad SAS exome AF: 0.000130

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000222

Gnomad OTH exome AF: 0.00210

GnomAD4 exome AF: 0.00222 AC: 3081 AN: 1390394 Hom.: 86 Cov.: 29 AF XY: 0.00195 AC XY: 1340 AN XY: 687048

Gnomad4 AFR exome AF: 0.0723

Gnomad4 AMR exome AF: 0.00399

Gnomad4 ASJ exome AF: 0.00330

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000188

Gnomad4 FIN exome AF: 0.0000271

Gnomad4 NFE exome AF: 0.000226

Gnomad4 OTH exome AF: 0.00461

GnomAD4 genome AF: 0.0196 AC: 2986 AN: 152364 Hom.: 101 Cov.: 33 AF XY: 0.0199 AC XY: 1480 AN XY: 74506

Gnomad4 AFR AF: 0.0673

Gnomad4 AMR AF: 0.00725

Gnomad4 ASJ AF: 0.00374

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000441

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.0109 Hom.: 9

Bravo AF: 0.0226

Asia WGS AF: 0.00289 AC: 10 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	-0.92
Cadd	Benign	0.37
Dann	Benign	0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs9306098; hg19: chr21-45750048;