rs11870

Variant names:

• chr21-44339162-C-A
• rs11870
• NM_004928.3:c.33G>T

Your query was ambiguous. Multiple possible variants found:

• chr21-44339162-C-A
• chr21-44339162-C-G
• chr21-44339162-C-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_004928.3(CFAP410):​c.33G>T​(p.Arg11Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000757 in 1,321,348 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R11R) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: CFAP410 NM_004928.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0680
• Publications: 0 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

ENSG00000232969 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BP7: Synonymous conserved (PhyloP=0.068 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP410	NM_004928.3	c.33G>T	p.Arg11Arg	synonymous_variant	Exon 1 of 7	ENST00000339818.9	NP_004919.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP410	ENST00000339818.9	c.33G>T	p.Arg11Arg	synonymous_variant	Exon 1 of 7	1	NM_004928.3	ENSP00000344566.4
CFAP410	ENST00000397956.7	c.33G>T	p.Arg11Arg	synonymous_variant	Exon 1 of 7	1		ENSP00000381047.3
CFAP410	ENST00000325223.7	c.33G>T	p.Arg11Arg	synonymous_variant	Exon 1 of 7	1		ENSP00000317302.7
ENSG00000232969	ENST00000426029.1	n.-214C>A		upstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.57e-7 AC: 1 AN: 1321348 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 651634

African (AFR) AF: 0.00 AC: 0 AN: 26622

American (AMR) AF: 0.00 AC: 0 AN: 25064

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23136

East Asian (EAS) AF: 0.00 AC: 0 AN: 28020

South Asian (SAS) AF: 0.00 AC: 0 AN: 71204

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46762

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5328

European-Non Finnish (NFE) AF: 9.61e-7 AC: 1 AN: 1041080

Other (OTH) AF: 0.00 AC: 0 AN: 54132

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	12
DANN	Benign	0.92
PhyloP100		0.068
PromoterAI		-0.081	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs11870; hg19: chr21-45759045;