21-42472636-C-T

Variant summary

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

The NM_080860.4(RSPH1):c.*182G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0906 in 477,058 control chromosomes in the GnomAD database, including 2,448 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.075 (649 hom., cov: 33)
  • Exomes 𝑓: 0.098 (1799 hom.)
• Consequence: RSPH1 NM_080860.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.305

Genes affected

RSPH1 (HGNC:12371): (radial spoke head component 1) This gene encodes a male meiotic metaphase chromosome-associated acidic protein. This gene is expressed in tissues with motile cilia or flagella, including the trachea, lungs, airway brushings, and testes. Mutations in this gene result in primary ciliary dyskinesia-24. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2014]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 21-42472636-C-T is Benign according to our data. Variant chr21-42472636-C-T is described in ClinVar as [Benign]. Clinvar id is 1271567.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RSPH1	NM_080860.4	c.*182G>A		3_prime_UTR_variant	9/9	ENST00000291536.8
RSPH1	NM_001286506.2	c.*182G>A		3_prime_UTR_variant	8/8
RSPH1	XM_005261208.3	c.*182G>A		3_prime_UTR_variant	7/7
RSPH1	XM_011529786.2	c.*182G>A		3_prime_UTR_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RSPH1	ENST00000291536.8	c.*182G>A		3_prime_UTR_variant	9/9	1	NM_080860.4	P1
RSPH1	ENST00000493019.1	n.2730G>A		non_coding_transcript_exon_variant	8/8	2

Frequencies

GnomAD3 genomes AF: 0.0753 AC: 11453 AN: 152176 Hom.: 647 Cov.: 33

Gnomad AFR AF: 0.0185

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.0871

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.0780

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.0933

Gnomad OTH AF: 0.0895

GnomAD4 exome AF: 0.0979 AC: 31782 AN: 324764 Hom.: 1799 Cov.: 4 AF XY: 0.100 AC XY: 17046 AN XY: 169802

Gnomad4 AFR exome AF: 0.0210

Gnomad4 AMR exome AF: 0.0777

Gnomad4 ASJ exome AF: 0.120

Gnomad4 EAS exome AF: 0.132

Gnomad4 SAS exome AF: 0.150

Gnomad4 FIN exome AF: 0.0719

Gnomad4 NFE exome AF: 0.0948

Gnomad4 OTH exome AF: 0.0974

GnomAD4 genome AF: 0.0753 AC: 11463 AN: 152294 Hom.: 649 Cov.: 33 AF XY: 0.0763 AC XY: 5681 AN XY: 74464

Gnomad4 AFR AF: 0.0184

Gnomad4 AMR AF: 0.0873

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.158

Gnomad4 FIN AF: 0.0780

Gnomad4 NFE AF: 0.0933

Gnomad4 OTH AF: 0.0956

Alfa AF: 0.0795 Hom.: 82

Bravo AF: 0.0740

Asia WGS AF: 0.141 AC: 490 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.7
Dann	Benign	0.53

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: rs1127455; hg19: chr21-43892746; COSMIC: COSV52320968; COSMIC: COSV52320968;