12-122001463-T-C

Variant names:

• chr12-122001463-T-C
• rs1182927
• NM_144668.6:c.3236-34T>C

Variant summary

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

The NM_144668.6(CFAP251):​c.3236-34T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.868 in 1,550,826 control chromosomes in the GnomAD database, including 586,059 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 0.88 (58812 hom., cov: 31)
  • Exomes 𝑓: 0.87 (527247 hom.)
• Consequence: CFAP251 NM_144668.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900
• Publications: 13 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

LOC124903038 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.936 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP251	NM_144668.6	c.3236-34T>C		intron_variant	Intron 20 of 21	ENST00000288912.9	NP_653269.3
LOC124903038	XR_007063499.1	n.89+4149A>G		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP251	ENST00000288912.9	c.3236-34T>C		intron_variant	Intron 20 of 21	1	NM_144668.6	ENSP00000288912.4
CFAP251	ENST00000428465.2	n.3060-34T>C		intron_variant	Intron 1 of 2	2
CFAP251	ENST00000545988.1	n.-241T>C		upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.878 AC: 133475 AN: 152002 Hom.: 58765 Cov.: 31

Gnomad AFR AF: 0.944

Gnomad AMI AF: 0.953

Gnomad AMR AF: 0.795

Gnomad ASJ AF: 0.895

Gnomad EAS AF: 0.855

Gnomad SAS AF: 0.858

Gnomad FIN AF: 0.807

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.869

Gnomad OTH AF: 0.868

GnomAD2 exomes AF: 0.847 AC: 211296 AN: 249502 AF XY: 0.851

Gnomad AFR exome AF: 0.947

Gnomad AMR exome AF: 0.725

Gnomad ASJ exome AF: 0.887

Gnomad EAS exome AF: 0.853

Gnomad FIN exome AF: 0.813

Gnomad NFE exome AF: 0.868

Gnomad OTH exome AF: 0.856

GnomAD4 exome AF: 0.867 AC: 1213171 AN: 1398706 Hom.: 527247 Cov.: 22 AF XY: 0.868 AC XY: 607377 AN XY: 699980

African (AFR) AF: 0.949 AC: 30607 AN: 32238

American (AMR) AF: 0.731 AC: 32649 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.888 AC: 22830 AN: 25714

East Asian (EAS) AF: 0.855 AC: 33675 AN: 39390

South Asian (SAS) AF: 0.857 AC: 72800 AN: 84942

European-Finnish (FIN) AF: 0.816 AC: 43530 AN: 53378

Middle Eastern (MID) AF: 0.893 AC: 5060 AN: 5666

European-Non Finnish (NFE) AF: 0.874 AC: 921233 AN: 1054486

Other (OTH) AF: 0.872 AC: 50787 AN: 58236

GnomAD4 genome AF: 0.878 AC: 133579 AN: 152120 Hom.: 58812 Cov.: 31 AF XY: 0.874 AC XY: 65005 AN XY: 74358

African (AFR) AF: 0.944 AC: 39193 AN: 41524

American (AMR) AF: 0.794 AC: 12131 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.895 AC: 3107 AN: 3472

East Asian (EAS) AF: 0.855 AC: 4413 AN: 5164

South Asian (SAS) AF: 0.858 AC: 4138 AN: 4822

European-Finnish (FIN) AF: 0.807 AC: 8532 AN: 10572

Middle Eastern (MID) AF: 0.895 AC: 263 AN: 294

European-Non Finnish (NFE) AF: 0.869 AC: 59098 AN: 67982

Other (OTH) AF: 0.870 AC: 1835 AN: 2108

Alfa AF: 0.855 Hom.: 18151

Bravo AF: 0.880

Asia WGS AF: 0.852 AC: 2962 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.1
DANN	Benign	0.70
PhyloP100		-0.0090
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: rs1182927; hg19: chr12-122439369;