12-121966027-A-G

Variant names:

• chr12-121966027-A-G
• rs1177589
• NM_144668.6:c.2493-928A>G

Variant summary

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

The NM_144668.6(CFAP251):​c.2493-928A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 151,506 control chromosomes in the GnomAD database, including 35,779 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 0.65 (35779 hom., cov: 27)
• Consequence: CFAP251 NM_144668.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.473
• Publications: 2 publications found

Genes affected

CFAP251 (HGNC:28506): (cilia and flagella associated protein 251) This protein encoded by this gene belongs to the WD repeat-containing family of proteins, which function in the formation of protein-protein complexes in a variety of biological pathways. This family member appears to function in the determination of mean platelet volume (MPV), and polymorphisms in this gene have been associated with variance in MPV. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Sep 2011]

CFAP251 Gene-Disease associations (from GenCC):

• spermatogenic failure 33

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• non-syndromic male infertility due to sperm motility disorder

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144668.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP251	NM_144668.6	MANE Select	c.2493-928A>G		intron	N/A	NP_653269.3
	CFAP251	NM_001178003.2		c.2493-928A>G		intron	N/A	NP_001171474.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP251	ENST00000288912.9	TSL:1 MANE Select	c.2493-928A>G		intron	N/A	ENSP00000288912.4
	CFAP251	ENST00000397454.2	TSL:1	c.2493-928A>G		intron	N/A	ENSP00000380595.2
	CFAP251	ENST00000545752.1	TSL:2	n.170-928A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.655 AC: 99194 AN: 151388 Hom.: 35773 Cov.: 27

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.889

Gnomad AMR AF: 0.682

Gnomad ASJ AF: 0.853

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.778

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.822

Gnomad OTH AF: 0.698

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

GnomAD4 genome AF: 0.655 AC: 99226 AN: 151506 Hom.: 35779 Cov.: 27 AF XY: 0.652 AC XY: 48266 AN XY: 74050

African (AFR) AF: 0.338 AC: 13951 AN: 41274

American (AMR) AF: 0.682 AC: 10384 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.853 AC: 2957 AN: 3466

East Asian (EAS) AF: 0.532 AC: 2722 AN: 5114

South Asian (SAS) AF: 0.573 AC: 2745 AN: 4792

European-Finnish (FIN) AF: 0.778 AC: 8147 AN: 10476

Middle Eastern (MID) AF: 0.803 AC: 236 AN: 294

European-Non Finnish (NFE) AF: 0.822 AC: 55804 AN: 67852

Other (OTH) AF: 0.701 AC: 1473 AN: 2100

Alfa AF: 0.703 Hom.: 5237

Bravo AF: 0.638

Asia WGS AF: 0.548 AC: 1907 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.3
DANN	Benign	0.66
PhyloP100		0.47
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: rs1177589; hg19: chr12-122403933;