rs41290844

Variant names:

• chr6-116629713-G-A
• rs41290844
• NM_001010892.3:c.1798+11G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-116629713-G-A
• chr6-116629713-G-C
• chr6-116629713-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001010892.3(RSPH4A):​c.1798+11G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0117 in 1,601,184 control chromosomes in the GnomAD database, including 155 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0080 (11 hom., cov: 32)
  • Exomes 𝑓: 0.012 (144 hom.)
• Consequence: RSPH4A NM_001010892.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.224
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 11

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics, ClinGen
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

LOC124901386 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 6-116629713-G-A is Benign according to our data. Variant chr6-116629713-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 227054.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00804 (1225/152278) while in subpopulation NFE AF = 0.0141 (959/68024). AF 95% confidence interval is 0.0134. There are 11 homozygotes in GnomAd4. There are 535 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 11 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010892.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSPH4A	NM_001010892.3	MANE Select	c.1798+11G>A		intron	N/A	NP_001010892.1	Q5TD94-1
	RSPH4A	NM_001161664.2		c.1663-722G>A		intron	N/A	NP_001155136.1	Q5TD94-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSPH4A	ENST00000229554.10	TSL:1 MANE Select	c.1798+11G>A		intron	N/A	ENSP00000229554.5	Q5TD94-1
	RSPH4A	ENST00000368581.8	TSL:1	c.1663-722G>A		intron	N/A	ENSP00000357570.4	Q5TD94-3
	RSPH4A	ENST00000368580.4	TSL:5	c.1057+11G>A		intron	N/A	ENSP00000357569.4	Q5TD94-2

Frequencies

GnomAD3 genomes AF: 0.00805 AC: 1225 AN: 152160 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.00220

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.00563

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00245

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0141

Gnomad OTH AF: 0.00718

GnomAD2 exomes AF: 0.00739 AC: 1836 AN: 248432 AF XY: 0.00726

Gnomad AFR exome AF: 0.00204

Gnomad AMR exome AF: 0.00307

Gnomad ASJ exome AF: 0.00308

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00330

Gnomad NFE exome AF: 0.0136

Gnomad OTH exome AF: 0.00524

GnomAD4 exome AF: 0.0121 AC: 17541 AN: 1448906 Hom.: 144 Cov.: 29 AF XY: 0.0119 AC XY: 8582 AN XY: 721856

African (AFR) AF: 0.00220 AC: 73 AN: 33122

American (AMR) AF: 0.00293 AC: 131 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00326 AC: 85 AN: 26052

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39586

South Asian (SAS) AF: 0.00223 AC: 192 AN: 85940

European-Finnish (FIN) AF: 0.00430 AC: 229 AN: 53238

Middle Eastern (MID) AF: 0.00109 AC: 6 AN: 5524

European-Non Finnish (NFE) AF: 0.0148 AC: 16252 AN: 1100826

Other (OTH) AF: 0.00955 AC: 572 AN: 59912

GnomAD4 genome AF: 0.00804 AC: 1225 AN: 152278 Hom.: 11 Cov.: 32 AF XY: 0.00718 AC XY: 535 AN XY: 74468

African (AFR) AF: 0.00219 AC: 91 AN: 41550

American (AMR) AF: 0.00562 AC: 86 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4826

European-Finnish (FIN) AF: 0.00245 AC: 26 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0141 AC: 959 AN: 68024

Other (OTH) AF: 0.00710 AC: 15 AN: 2112

Alfa AF: 0.00733 Hom.: 5

Bravo AF: 0.00836

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Primary ciliary dyskinesia (1)
-	-	1	Primary ciliary dyskinesia 11 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.87
DANN	Benign	0.87
PhyloP100		-0.22
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs41290844; hg19: chr6-116950876;