rs7961894

Variant names:

• chr12-121927677-C-T
• rs7961894
• NM_144668.6:c.747+3687C>T

Variant summary

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

The NM_144668.6(CFAP251):​c.747+3687C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0721 in 152,180 control chromosomes in the GnomAD database, including 503 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 0.072 (503 hom., cov: 31)
• Consequence: CFAP251 NM_144668.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.260
• Publications: 57 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP251	NM_144668.6	c.747+3687C>T		intron_variant	Intron 3 of 21	ENST00000288912.9	NP_653269.3
CFAP251	NM_001178003.2	c.747+3687C>T		intron_variant	Intron 3 of 17		NP_001171474.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP251	ENST00000288912.9	c.747+3687C>T		intron_variant	Intron 3 of 21	1	NM_144668.6	ENSP00000288912.4
CFAP251	ENST00000397454.2	c.747+3687C>T		intron_variant	Intron 3 of 17	1		ENSP00000380595.2
CFAP251	ENST00000540779.1	n.645+3687C>T		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.0722 AC: 10981 AN: 152062 Hom.: 503 Cov.: 31

Gnomad AFR AF: 0.0197

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.0775

Gnomad ASJ AF: 0.0985

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0321

Gnomad FIN AF: 0.0949

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.0693

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

GnomAD4 genome AF: 0.0721 AC: 10979 AN: 152180 Hom.: 503 Cov.: 31 AF XY: 0.0715 AC XY: 5317 AN XY: 74380

African (AFR) AF: 0.0197 AC: 818 AN: 41550

American (AMR) AF: 0.0774 AC: 1182 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0985 AC: 342 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.0315 AC: 152 AN: 4820

European-Finnish (FIN) AF: 0.0949 AC: 1004 AN: 10582

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7186 AN: 67998

Other (OTH) AF: 0.0686 AC: 145 AN: 2114

Alfa AF: 0.0939 Hom.: 3217

Bravo AF: 0.0701

Asia WGS AF: 0.0160 AC: 57 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.2
DANN	Benign	0.38
PhyloP100		0.26
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: rs7961894; hg19: chr12-122365583;