Variant rs10485188 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001010892.3(RSPH4A):c.1916+46C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0546 in 889,158 control chromosomes in the GnomAD database, including 2,269 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.061 ( 381 hom., cov: 31)

Exomes 𝑓: 0.053 ( 1888 hom. )

Consequence

RSPH4A
NM_001010892.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0930

Variant links:

Genes affected

RSPH4A (HGNC:21558): (radial spoke head component 4A) This gene encodes a protein that appears to be a component the radial spoke head, as determined by homology to similar proteins in the biflagellate alga Chlamydomonas reinhardtii and other ciliates. Radial spokes, which are regularly spaced along cilia, sperm, and flagella axonemes, consist of a thin 'stalk' and a bulbous 'head' that form a signal transduction scaffold between the central pair of microtubules and dynein. Mutations in this gene cause primary ciliary dyskinesia 1, a disease arising from dysmotility of motile cilia and sperm. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

RSPH4A links:

LOC124901386 (HGNC:):

LOC124901386 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 6-116630598-C-G is Benign according to our data. Variant chr6-116630598-C-G is described in ClinVar as [Benign]. Clinvar id is 257050.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSPH4A	NM_001010892.3 linkuse as main transcript	c.1916+46C>G		intron_variant		ENST00000229554.10	NP_001010892.1
LOC124901386	XR_007059721.1 linkuse as main transcript	n.460-608G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
RSPH4A	ENST00000229554.10 linkuse as main transcript	c.1916+46C>G	intron_variant	1	NM_001010892.3	ENSP00000229554	P1	Q5TD94-1
RSPH4A	ENST00000368581.8 linkuse as main transcript	c.1780+46C>G	intron_variant	1		ENSP00000357570		Q5TD94-3
RSPH4A	ENST00000368580.4 linkuse as main transcript	c.1175+46C>G	intron_variant	5		ENSP00000357569		Q5TD94-2

Frequencies

GnomAD3 genomes

AF:

0.0606

AC:

9124

AN:

150492

Hom.:

379

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0714

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.147

Gnomad ASJ

AF:

0.0531

Gnomad EAS

AF:

0.0205

Gnomad SAS

AF:

0.0540

Gnomad FIN

AF:

0.0283

Gnomad MID

AF:

0.0318

Gnomad NFE

AF:

0.0445

Gnomad OTH

AF:

0.0673

GnomAD3 exomes

AF:

0.0711

AC:

17836

AN:

250998

Hom.:

1222

AF XY:

0.0648

AC XY:

8797

AN XY:

135698

show subpopulations

Gnomad AFR exome

AF:

0.0740

Gnomad AMR exome

AF:

0.230

Gnomad ASJ exome

AF:

0.0473

Gnomad EAS exome

AF:

0.0173

Gnomad SAS exome

AF:

0.0561

Gnomad FIN exome

AF:

0.0301

Gnomad NFE exome

AF:

0.0452

Gnomad OTH exome

AF:

0.0672

GnomAD4 exome

AF:

0.0534

AC:

39424

AN:

738558

Hom.:

1888

Cov.:

AF XY:

0.0512

AC XY:

20245

AN XY:

395362

show subpopulations

Gnomad4 AFR exome

AF:

0.0749

Gnomad4 AMR exome

AF:

0.224

Gnomad4 ASJ exome

AF:

0.0490

Gnomad4 EAS exome

AF:

0.0238

Gnomad4 SAS exome

AF:

0.0532

Gnomad4 FIN exome

AF:

0.0301

Gnomad4 NFE exome

AF:

0.0415

Gnomad4 OTH exome

AF:

0.0540

GnomAD4 genome

AF:

0.0607

AC:

9139

AN:

150600

Hom.:

381

Cov.:

AF XY:

0.0601

AC XY:

4410

AN XY:

73416

show subpopulations

Gnomad4 AFR

AF:

0.0714

Gnomad4 AMR

AF:

0.147

Gnomad4 ASJ

AF:

0.0531

Gnomad4 EAS

AF:

0.0208

Gnomad4 SAS

AF:

0.0543

Gnomad4 FIN

AF:

0.0283

Gnomad4 NFE

AF:

0.0445

Gnomad4 OTH

AF:

0.0667

Alfa

AF:

0.0500

Hom.:

Bravo

AF:

0.0745

Asia WGS

AF:

0.0430

AC:

152

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 06, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

6.9

DANN

Benign

0.68

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