rs8111071

Positions:

• chr19-45804148-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030785.4(RSPH6A):​c.1653+104T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0746 in 851,118 control chromosomes in the GnomAD database, including 2,887 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.061 (391 hom., cov: 32)
  • Exomes 𝑓: 0.078 (2496 hom.)
• Consequence: RSPH6A NM_030785.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82

Genes affected

RSPH6A (HGNC:14241): (radial spoke head 6 homolog A) The protein encoded by this gene is similar to a sea urchin radial spoke head protein. Radial spoke protein complexes form part of the axoneme of eukaryotic flagella and are located between the axoneme's outer ring of doublet microtubules and central pair of microtubules. In Chlamydomonas, radial spoke proteins are thought to regulate the activity of dynein and the symmetry of flagellar bending patterns. This gene maps to a region of chromosome 19 that is linked to primary ciliary dyskinesia-2 (CILD2). [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.09 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSPH6A	NM_030785.4	c.1653+104T>C		intron_variant		ENST00000221538.8	NP_110412.1
RSPH6A	XM_011527351.3	c.1653+104T>C		intron_variant			XP_011525653.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSPH6A	ENST00000221538.8	c.1653+104T>C		intron_variant		1	NM_030785.4	ENSP00000221538	P1
RSPH6A	ENST00000597055.1	c.1653+104T>C		intron_variant		1		ENSP00000472630
RSPH6A	ENST00000600188.5	c.861+104T>C		intron_variant		2		ENSP00000471559

Frequencies

GnomAD3 genomes AF: 0.0606 AC: 9229 AN: 152170 Hom.: 391 Cov.: 32

Gnomad AFR AF: 0.0144

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.0547

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0611

Gnomad FIN AF: 0.0369

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.0919

Gnomad OTH AF: 0.0774

GnomAD4 exome AF: 0.0776 AC: 54258 AN: 698830 Hom.: 2496 AF XY: 0.0780 AC XY: 27925 AN XY: 358144

Gnomad4 AFR exome AF: 0.0125

Gnomad4 AMR exome AF: 0.0498

Gnomad4 ASJ exome AF: 0.144

Gnomad4 EAS exome AF: 0.000234

Gnomad4 SAS exome AF: 0.0710

Gnomad4 FIN exome AF: 0.0382

Gnomad4 NFE exome AF: 0.0877

Gnomad4 OTH exome AF: 0.0793

GnomAD4 genome AF: 0.0606 AC: 9223 AN: 152288 Hom.: 391 Cov.: 32 AF XY: 0.0573 AC XY: 4265 AN XY: 74474

Gnomad4 AFR AF: 0.0143

Gnomad4 AMR AF: 0.0546

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.0618

Gnomad4 FIN AF: 0.0369

Gnomad4 NFE AF: 0.0919

Gnomad4 OTH AF: 0.0766

Alfa AF: 0.0867 Hom.: 1339

Bravo AF: 0.0589

Asia WGS AF: 0.0270 AC: 96 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.21
DANN	Benign	0.27

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: rs8111071; hg19: chr19-46307406; COSMIC: COSV55572430;