rs11552068

Variant names:

• chr21-44330285-A-G
• rs11552068
• NM_004928.3:c.684T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001271441.2(CFAP410):​c.1041T>C​(p.Asp347Asp) 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_001271441.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.228
• 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 Classification: SUPPORTIVE Submitted by: Orphanet
• cone-rod dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000241728 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001271441.2. 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.684T>C	p.Asp228Asp	synonymous	Exon 7 of 7	NP_004919.1
	CFAP410	NM_001271441.2		c.1041T>C	p.Asp347Asp	synonymous	Exon 7 of 7	NP_001258370.1
	CFAP410	NM_001271440.2		c.681T>C	p.Asp227Asp	synonymous	Exon 7 of 7	NP_001258369.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP410	ENST00000339818.9	TSL:1 MANE Select	c.684T>C	p.Asp228Asp	synonymous	Exon 7 of 7	ENSP00000344566.4
	CFAP410	ENST00000397956.7	TSL:1	c.1041T>C	p.Asp347Asp	synonymous	Exon 7 of 7	ENSP00000381047.3
	CFAP410	ENST00000325223.7	TSL:1	c.681T>C	p.Asp227Asp	synonymous	Exon 7 of 7	ENSP00000317302.7

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

GnomAD2 exomes AF: 0.0182 AC: 4276 AN: 234990 AF XY: 0.0139

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 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

African (AFR) AF: 0.128 AC: 4287 AN: 33446

American (AMR) AF: 0.0479 AC: 2127 AN: 44450

Ashkenazi Jewish (ASJ) AF: 0.0000384 AC: 1 AN: 26058

East Asian (EAS) AF: 0.0229 AC: 908 AN: 39626

South Asian (SAS) AF: 0.00117 AC: 100 AN: 85782

European-Finnish (FIN) AF: 0.00455 AC: 232 AN: 50992

Middle Eastern (MID) AF: 0.0153 AC: 88 AN: 5760

European-Non Finnish (NFE) AF: 0.000248 AC: 276 AN: 1110896

Other (OTH) AF: 0.0143 AC: 861 AN: 60240

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

African (AFR) AF: 0.121 AC: 5045 AN: 41536

American (AMR) AF: 0.0306 AC: 468 AN: 15308

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

East Asian (EAS) AF: 0.0293 AC: 152 AN: 5184

South Asian (SAS) AF: 0.00186 AC: 9 AN: 4826

European-Finnish (FIN) AF: 0.00490 AC: 52 AN: 10622

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

European-Non Finnish (NFE) AF: 0.000544 AC: 37 AN: 68026

Other (OTH) AF: 0.0355 AC: 75 AN: 2112

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.6
DANN	Benign	0.68
PhyloP100		0.23
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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: rs11552068; hg19: chr21-45750168;