21-32601798-T-A

Position:

• chr21-32601798-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_021254.4(CFAP298):​c.*65A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0351 in 805,666 control chromosomes in the GnomAD database, including 525 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.043 (129 hom., cov: 31)
  • Exomes 𝑓: 0.033 (396 hom.)
• Consequence: CFAP298 NM_021254.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.18

Genes affected

CFAP298 (HGNC:1301): (cilia and flagella associated protein 298) This gene encodes a protein that plays a critical role in dynein arm assembly and motile cilia function. Mutations in this gene result in primary ciliary dyskinesia. Naturally occuring readthrough transcription occurs from this locus to the downstream t-complex 10 like (TCP10L) gene. [provided by RefSeq, Apr 2017]

CFAP298-TCP10L (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 21-32601798-T-A is Benign according to our data. Variant chr21-32601798-T-A is described in ClinVar as [Benign]. Clinvar id is 1270433.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP298	NM_021254.4	c.*65A>T		3_prime_UTR_variant	7/7	ENST00000290155.8	NP_067077.1
CFAP298-TCP10L	NR_146638.2	n.800+1363A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP298	ENST00000290155.8	c.*65A>T		3_prime_UTR_variant	7/7	1	NM_021254.4	ENSP00000290155	P1

Frequencies

GnomAD3 genomes AF: 0.0425 AC: 6450 AN: 151664 Hom.: 127 Cov.: 31

Gnomad AFR AF: 0.0558

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0331

Gnomad ASJ AF: 0.0536

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0591

Gnomad FIN AF: 0.0240

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0412

Gnomad OTH AF: 0.0431

GnomAD4 exome AF: 0.0334 AC: 21848 AN: 653894 Hom.: 396 Cov.: 9 AF XY: 0.0354 AC XY: 12242 AN XY: 346138

Gnomad4 AFR exome AF: 0.0511

Gnomad4 AMR exome AF: 0.0263

Gnomad4 ASJ exome AF: 0.0498

Gnomad4 EAS exome AF: 0.000259

Gnomad4 SAS exome AF: 0.0601

Gnomad4 FIN exome AF: 0.0217

Gnomad4 NFE exome AF: 0.0323

Gnomad4 OTH exome AF: 0.0368

GnomAD4 genome AF: 0.0426 AC: 6465 AN: 151772 Hom.: 129 Cov.: 31 AF XY: 0.0425 AC XY: 3157 AN XY: 74224

Gnomad4 AFR AF: 0.0560

Gnomad4 AMR AF: 0.0330

Gnomad4 ASJ AF: 0.0536

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0598

Gnomad4 FIN AF: 0.0240

Gnomad4 NFE AF: 0.0412

Gnomad4 OTH AF: 0.0426

Alfa AF: 0.0394 Hom.: 10

Bravo AF: 0.0436

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 15, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.027
DANN	Benign	0.10

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1043330; hg19: chr21-33974108;