rs41281830

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_152732.5(RSPH9):c.671-4259C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0254 in 1,522,248 control chromosomes in the GnomAD database, including 584 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 42 hom., cov: 32)

Exomes 𝑓: 0.026 ( 542 hom. )

Consequence

RSPH9
NM_152732.5 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.01

Variant links:

Genes affected

RSPH9 (HGNC:21057): (radial spoke head component 9) This gene encodes a protein thought to be a component of the radial spoke head in motile cilia and flagella. Mutations in this gene are associated with primary ciliary dyskinesia 12. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Jul 2010]

RSPH9 links:

POLR1C (HGNC:):

POLR1C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 6-43666530-C-T is Benign according to our data. Variant chr6-43666530-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 165064.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-43666530-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0182 (2764/152248) while in subpopulation SAS AF= 0.033 (159/4822). AF 95% confidence interval is 0.0288. There are 42 homozygotes in gnomad4. There are 1265 alleles in male gnomad4 subpopulation. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 42 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
RSPH9	NM_152732.5 linkuse as main transcript	c.671-4259C>T	intron_variant	ENST00000372163.5
RSPH9	NM_001193341.2 linkuse as main transcript	c.722+10C>T	intron_variant
POLR1C	NM_001318876.2 linkuse as main transcript	c.945+137259C>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RSPH9	ENST00000372163.5 linkuse as main transcript	c.671-4259C>T		intron_variant		1	NM_152732.5	P1	Q9H1X1-1
RSPH9	ENST00000372165.8 linkuse as main transcript	c.722+10C>T		intron_variant		2			Q9H1X1-2

Frequencies

GnomAD3 genomes

AF:

0.0182

AC:

2765

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00514

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.0187

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.00270

Gnomad SAS

AF:

0.0332

Gnomad FIN

AF:

0.00424

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0288

Gnomad OTH

AF:

0.0187

GnomAD3 exomes

AF:

0.0193

AC:

2802

AN:

145468

Hom.:

AF XY:

0.0202

AC XY:

1582

AN XY:

78424

show subpopulations

Gnomad AFR exome

AF:

0.00416

Gnomad AMR exome

AF:

0.0162

Gnomad ASJ exome

AF:

0.00853

Gnomad EAS exome

AF:

0.00197

Gnomad SAS exome

AF:

0.0296

Gnomad FIN exome

AF:

0.00383

Gnomad NFE exome

AF:

0.0282

Gnomad OTH exome

AF:

0.0192

GnomAD4 exome

AF:

0.0262

AC:

35860

AN:

1370000

Hom.:

542

Cov.:

AF XY:

0.0262

AC XY:

17713

AN XY:

677188

show subpopulations

Gnomad4 AFR exome

AF:

0.00436

Gnomad4 AMR exome

AF:

0.0165

Gnomad4 ASJ exome

AF:

0.00893

Gnomad4 EAS exome

AF:

0.000760

Gnomad4 SAS exome

AF:

0.0287

Gnomad4 FIN exome

AF:

0.00591

Gnomad4 NFE exome

AF:

0.0294

Gnomad4 OTH exome

AF:

0.0237

GnomAD4 genome

AF:

0.0182

AC:

2764

AN:

152248

Hom.:

Cov.:

AF XY:

0.0170

AC XY:

1265

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.00510

Gnomad4 AMR

AF:

0.0186

Gnomad4 ASJ

AF:

0.0101

Gnomad4 EAS

AF:

0.00270

Gnomad4 SAS

AF:

0.0330

Gnomad4 FIN

AF:

0.00424

Gnomad4 NFE

AF:

0.0288

Gnomad4 OTH

AF:

0.0185

Alfa

AF:

0.0226

Hom.:

Bravo

AF:

0.0177

Asia WGS

AF:

0.0260

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Feb 21, 2013

722+10C>T in intron 5 of RSPH9: This variant is not expected to have clinical si gnificance because it is not located within the conserved splice consensus seque nce. It has been identified in 4.5% (8/178) of English and Scottish chromosomes from a broad population by the 1000 Genomes Project (http://www.ncbi.nlm.nih.gov /projects/SNP; dbSNP rs41281830). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 06, 2019

- -

Primary ciliary dyskinesia 12

Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Nov 22, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

Cadd

Benign

0.21

Dann

Benign

0.54

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over