7-90271725-A-C

Position:

• chr7-90271725-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001039706.3(CFAP69):​c.682+50A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.865 in 1,588,948 control chromosomes in the GnomAD database, including 595,957 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.90 (61709 hom., cov: 33)
  • Exomes 𝑓: 0.86 (534248 hom.)
• Consequence: CFAP69 NM_001039706.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.01

Genes affected

CFAP69 (HGNC:26107): (cilia and flagella associated protein 69) Acts upstream of or within sperm axoneme assembly. Located in cytoplasm and sperm midpiece. Implicated in spermatogenic failure 24. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 7-90271725-A-C is Benign according to our data. Variant chr7-90271725-A-C is described in ClinVar as [Benign]. Clinvar id is 1192634.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFAP69	NM_001039706.3	c.682+50A>C		intron_variant		ENST00000389297.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFAP69	ENST00000389297.8	c.682+50A>C		intron_variant		1	NM_001039706.3	P1

Frequencies

GnomAD3 genomes AF: 0.898 AC: 136608 AN: 152054 Hom.: 61652 Cov.: 33

Gnomad AFR AF: 0.971

Gnomad AMI AF: 0.855

Gnomad AMR AF: 0.884

Gnomad ASJ AF: 0.847

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.942

Gnomad FIN AF: 0.908

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.849

Gnomad OTH AF: 0.883

GnomAD3 exomes AF: 0.891 AC: 208404 AN: 233884 Hom.: 93132 AF XY: 0.888 AC XY: 112618 AN XY: 126798

Gnomad AFR exome AF: 0.975

Gnomad AMR exome AF: 0.905

Gnomad ASJ exome AF: 0.842

Gnomad EAS exome AF: 0.999

Gnomad SAS exome AF: 0.929

Gnomad FIN exome AF: 0.909

Gnomad NFE exome AF: 0.850

Gnomad OTH exome AF: 0.879

GnomAD4 exome AF: 0.861 AC: 1237580 AN: 1436776 Hom.: 534248 Cov.: 33 AF XY: 0.862 AC XY: 614385 AN XY: 712426

Gnomad4 AFR exome AF: 0.976

Gnomad4 AMR exome AF: 0.903

Gnomad4 ASJ exome AF: 0.837

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.928

Gnomad4 FIN exome AF: 0.905

Gnomad4 NFE exome AF: 0.844

Gnomad4 OTH exome AF: 0.875

GnomAD4 genome AF: 0.898 AC: 136725 AN: 152172 Hom.: 61709 Cov.: 33 AF XY: 0.902 AC XY: 67141 AN XY: 74398

Gnomad4 AFR AF: 0.971

Gnomad4 AMR AF: 0.884

Gnomad4 ASJ AF: 0.847

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.942

Gnomad4 FIN AF: 0.908

Gnomad4 NFE AF: 0.849

Gnomad4 OTH AF: 0.884

Alfa AF: 0.863 Hom.: 7385

Bravo AF: 0.897

Asia WGS AF: 0.970 AC: 3369 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Spermatogenic failure 24 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.47
DANN	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs10280053; hg19: chr7-89901039;