12-121957871-A-G

Variant names:

• chr12-121957871-A-G
• rs830124
• NM_144668.6:c.1731-401A>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.1731-401A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.858 in 152,106 control chromosomes in the GnomAD database, including 56,071 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 0.86 (56071 hom., cov: 31)
• Consequence: CFAP251 NM_144668.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.266
• Publications: 18 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.872 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.1731-401A>G		intron	N/A	NP_653269.3
	CFAP251	NM_001178003.2		c.1731-401A>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.1731-401A>G		intron	N/A	ENSP00000288912.4
	CFAP251	ENST00000397454.2	TSL:1	c.1731-401A>G		intron	N/A	ENSP00000380595.2
	CFAP251	ENST00000535257.1	TSL:3	n.1836-401A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.858 AC: 130443 AN: 151988 Hom.: 56036 Cov.: 31

Gnomad AFR AF: 0.880

Gnomad AMI AF: 0.927

Gnomad AMR AF: 0.787

Gnomad ASJ AF: 0.900

Gnomad EAS AF: 0.817

Gnomad SAS AF: 0.854

Gnomad FIN AF: 0.808

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.869

Gnomad OTH AF: 0.854

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

GnomAD4 genome AF: 0.858 AC: 130527 AN: 152106 Hom.: 56071 Cov.: 31 AF XY: 0.855 AC XY: 63602 AN XY: 74350

African (AFR) AF: 0.880 AC: 36500 AN: 41492

American (AMR) AF: 0.787 AC: 12020 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.900 AC: 3124 AN: 3472

East Asian (EAS) AF: 0.816 AC: 4229 AN: 5180

South Asian (SAS) AF: 0.854 AC: 4109 AN: 4814

European-Finnish (FIN) AF: 0.808 AC: 8540 AN: 10566

Middle Eastern (MID) AF: 0.874 AC: 257 AN: 294

European-Non Finnish (NFE) AF: 0.869 AC: 59101 AN: 67990

Other (OTH) AF: 0.856 AC: 1803 AN: 2106

Alfa AF: 0.864 Hom.: 178553

Bravo AF: 0.857

Asia WGS AF: 0.830 AC: 2884 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.88
DANN	Benign	0.75
PhyloP100		-0.27
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: rs830124; hg19: chr12-122395777;