rs10485188

chr6-116630598-C-Gchr6-116630598-C-T

Variant summary

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

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0930

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]

LOC124901386 (HGNC:):

ACMG classification

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	UniProt
RSPH4A	NM_001010892.3	c.1916+46C>G		intron_variant		ENST00000229554.10
LOC124901386	XR_007059721.1	n.460-608G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RSPH4A	ENST00000229554.10	c.1916+46C>G		intron_variant		1	NM_001010892.3	P1
RSPH4A	ENST00000368581.8	c.1780+46C>G		intron_variant		1
RSPH4A	ENST00000368580.4	c.1175+46C>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0606 AC: 9124 AN: 150492 Hom.: 379 Cov.: 31

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

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.: 10 AF XY: 0.0512 AC XY: 20245 AN XY: 395362

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.: 31 AF XY: 0.0601 AC XY: 4410 AN XY: 73416

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.: 47

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

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

Other links and lift over

dbSNP: rs10485188; hg19: chr6-116951761;