NM_001271049.2:c.527+2127A>G

Variant names:

• chr2-119564241-A-G
• rs2587695
• NM_001271049.2:c.527+2127A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001271049.2(CFAP221):​c.527+2127A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 151,976 control chromosomes in the GnomAD database, including 26,407 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.58 (26407 hom., cov: 31)
• Consequence: CFAP221 NM_001271049.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.160
• Publications: 27 publications found

Genes affected

CFAP221 (HGNC:33720): (cilia and flagella associated protein 221) Predicted to enable calmodulin binding activity. Predicted to be involved in cilium assembly. Predicted to act upstream of or within cerebrospinal fluid circulation; motile cilium assembly; and mucociliary clearance. Predicted to be located in axoneme; extracellular region; and sperm flagellum. [provided by Alliance of Genome Resources, Apr 2022]

CFAP221 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia

  Inheritance: AD, AR Classification: MODERATE, SUPPORTIVE, LIMITED Submitted by: Orphanet, ClinGen, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.716 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP221	NM_001271049.2	c.527+2127A>G		intron_variant	Intron 6 of 23	ENST00000413369.8	NP_001257978.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP221	ENST00000413369.8	c.527+2127A>G		intron_variant	Intron 6 of 23	5	NM_001271049.2	ENSP00000393222.2

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88418 AN: 151858 Hom.: 26367 Cov.: 31

Gnomad AFR AF: 0.682

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.735

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.697

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.547

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.582 AC: 88512 AN: 151976 Hom.: 26407 Cov.: 31 AF XY: 0.590 AC XY: 43781 AN XY: 74254

African (AFR) AF: 0.682 AC: 28246 AN: 41432

American (AMR) AF: 0.556 AC: 8496 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1550 AN: 3470

East Asian (EAS) AF: 0.736 AC: 3791 AN: 5152

South Asian (SAS) AF: 0.560 AC: 2699 AN: 4816

European-Finnish (FIN) AF: 0.697 AC: 7351 AN: 10554

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.511 AC: 34742 AN: 67946

Other (OTH) AF: 0.544 AC: 1151 AN: 2114

Alfa AF: 0.530 Hom.: 95957

Bravo AF: 0.579

Asia WGS AF: 0.649 AC: 2255 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	5.8
DANN	Benign	0.67
PhyloP100		0.16
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: rs2587695; hg19: chr2-120321817;