NM_004928.3:c.*30C>T

Variant names:

• chr21-44330168-G-A
• rs111631573
• NM_004928.3:c.*30C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004928.3(CFAP410):​c.*30C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00284 in 1,544,436 control chromosomes in the GnomAD database, including 127 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.016 (70 hom., cov: 33)
  • Exomes 𝑓: 0.0014 (57 hom.)
• Consequence: CFAP410 NM_004928.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.142
• Publications: 2 publications found

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]

CFAP410 Gene-Disease associations (from GenCC):

• axial spondylometaphyseal dysplasia

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• amyotrophic lateral sclerosis

  Inheritance: AD, SD Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, ClinGen
• cone-rod dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000241728 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 21-44330168-G-A is Benign according to our data. Variant chr21-44330168-G-A is described in ClinVar as Benign. ClinVar VariationId is 1221564.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0524 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004928.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP410	NM_004928.3	MANE Select	c.*30C>T		3_prime_UTR	Exon 7 of 7	NP_004919.1	O43822-1
	CFAP410	NM_001271441.2		c.*30C>T		3_prime_UTR	Exon 7 of 7	NP_001258370.1	O43822-4
	CFAP410	NM_001271440.2		c.*30C>T		3_prime_UTR	Exon 7 of 7	NP_001258369.1	O43822-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP410	ENST00000339818.9	TSL:1 MANE Select	c.*30C>T		3_prime_UTR	Exon 7 of 7	ENSP00000344566.4	O43822-1
	CFAP410	ENST00000397956.7	TSL:1	c.*30C>T		3_prime_UTR	Exon 7 of 7	ENSP00000381047.3	O43822-4
	CFAP410	ENST00000325223.7	TSL:1	c.*30C>T		3_prime_UTR	Exon 7 of 7	ENSP00000317302.7	O43822-3

Frequencies

GnomAD3 genomes AF: 0.0157 AC: 2384 AN: 152240 Hom.: 70 Cov.: 33

Gnomad AFR AF: 0.0543

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00667

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.0110

GnomAD2 exomes AF: 0.00354 AC: 525 AN: 148366 AF XY: 0.00285

Gnomad AFR exome AF: 0.0529

Gnomad AMR exome AF: 0.00285

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000118

Gnomad OTH exome AF: 0.00301

GnomAD4 exome AF: 0.00144 AC: 2005 AN: 1392078 Hom.: 57 Cov.: 29 AF XY: 0.00123 AC XY: 847 AN XY: 688046

African (AFR) AF: 0.0512 AC: 1637 AN: 31944

American (AMR) AF: 0.00356 AC: 131 AN: 36754

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25176

East Asian (EAS) AF: 0.00 AC: 0 AN: 36250

South Asian (SAS) AF: 0.000176 AC: 14 AN: 79734

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37322

Middle Eastern (MID) AF: 0.00144 AC: 6 AN: 4162

European-Non Finnish (NFE) AF: 0.0000369 AC: 40 AN: 1082778

Other (OTH) AF: 0.00305 AC: 177 AN: 57958

GnomAD4 genome AF: 0.0157 AC: 2388 AN: 152358 Hom.: 70 Cov.: 33 AF XY: 0.0147 AC XY: 1097 AN XY: 74502

African (AFR) AF: 0.0543 AC: 2256 AN: 41582

American (AMR) AF: 0.00666 AC: 102 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68036

Other (OTH) AF: 0.0109 AC: 23 AN: 2110

Alfa AF: 0.00680 Hom.: 9

Bravo AF: 0.0178

Asia WGS AF: 0.00231 AC: 9 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.83
PhyloP100		-0.14
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs111631573; hg19: chr21-45750051;