rs2277809

chr21-44331939-G-A

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.449C>T(p.Thr150Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0288 in 1,613,518 control chromosomes in the GnomAD database, including 912 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.021 (51 hom., cov: 33)
  • Exomes 𝑓: 0.030 (861 hom.)
• Consequence: CFAP410 NM_004928.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.599

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=0.0021091402).
• BP6: Variant 21-44331939-G-A is Benign according to our data. Variant chr21-44331939-G-A is described in ClinVar as [Benign]. Clinvar id is 259587.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFAP410	NM_004928.3	c.449C>T	p.Thr150Ile	missense_variant	5/7	ENST00000339818.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFAP410	ENST00000339818.9	c.449C>T	p.Thr150Ile	missense_variant	5/7	1	NM_004928.3	P4
	ENST00000448927.1	n.706G>A		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes AF: 0.0211 AC: 3211 AN: 152244 Hom.: 51 Cov.: 33

Gnomad AFR AF: 0.00753

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.0184

Gnomad ASJ AF: 0.0311

Gnomad EAS AF: 0.0544

Gnomad SAS AF: 0.0715

Gnomad FIN AF: 0.00743

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0247

Gnomad OTH AF: 0.0239

GnomAD3 exomes AF: 0.0290 AC: 7244 AN: 249586 Hom.: 175 AF XY: 0.0316 AC XY: 4275 AN XY: 135258

Gnomad AFR exome AF: 0.00633

Gnomad AMR exome AF: 0.0161

Gnomad ASJ exome AF: 0.0361

Gnomad EAS exome AF: 0.0573

Gnomad SAS exome AF: 0.0672

Gnomad FIN exome AF: 0.00850

Gnomad NFE exome AF: 0.0246

Gnomad OTH exome AF: 0.0294

GnomAD4 exome AF: 0.0296 AC: 43279 AN: 1461156 Hom.: 861 Cov.: 31 AF XY: 0.0310 AC XY: 22556 AN XY: 726844

Gnomad4 AFR exome AF: 0.00574

Gnomad4 AMR exome AF: 0.0160

Gnomad4 ASJ exome AF: 0.0358

Gnomad4 EAS exome AF: 0.0640

Gnomad4 SAS exome AF: 0.0662

Gnomad4 FIN exome AF: 0.00870

Gnomad4 NFE exome AF: 0.0275

Gnomad4 OTH exome AF: 0.0322

GnomAD4 genome AF: 0.0211 AC: 3210 AN: 152362 Hom.: 51 Cov.: 33 AF XY: 0.0211 AC XY: 1570 AN XY: 74508

Gnomad4 AFR AF: 0.00750

Gnomad4 AMR AF: 0.0184

Gnomad4 ASJ AF: 0.0311

Gnomad4 EAS AF: 0.0544

Gnomad4 SAS AF: 0.0718

Gnomad4 FIN AF: 0.00743

Gnomad4 NFE AF: 0.0247

Gnomad4 OTH AF: 0.0236

Alfa AF: 0.0272 Hom.: 140

Bravo AF: 0.0211

TwinsUK AF: 0.0334 AC: 124

ALSPAC AF: 0.0267 AC: 103

ESP6500AA AF: 0.00976 AC: 43

ESP6500EA AF: 0.0280 AC: 241

ExAC AF: 0.0295 AC: 3575

Asia WGS AF: 0.0490 AC: 171 AN: 3478

EpiCase AF: 0.0304

EpiControl AF: 0.0299

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
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.64
Cadd	Benign	1.8
Dann	Benign	0.93
DEOGEN2	Benign	0.014	T;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.65	T;T;T
MetaRNN	Benign	0.0021	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N;N;N
PROVEAN	Benign	-1.6	N;N;N
REVEL	Benign	0.096
Sift	Benign	0.43	T;T;T
Sift4G	Benign	0.25	T;T;T
Polyphen		0.54	P;.;.
Vest4		0.080
MPC		0.11
ClinPred		0.0058	T
GERP RS		-3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.032
gMVP		0.23

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: rs2277809; hg19: chr21-45751822; COSMIC: COSV57394642; COSMIC: COSV57394642;