rs111759882

Variant names:

• chr21-42472629-G-A
• rs111759882
• NM_080860.4:c.*189C>T

Your query was ambiguous. Multiple possible variants found:

• chr21-42472629-G-A
• chr21-42472629-G-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_080860.4(RSPH1):​c.*189C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00251 in 451,656 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0059 (10 hom., cov: 33)
  • Exomes 𝑓: 0.00077 (2 hom.)
• Consequence: RSPH1 NM_080860.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.571
• Publications: 1 publications found

Genes affected

RSPH1 (HGNC:12371): (radial spoke head component 1) This gene encodes a male meiotic metaphase chromosome-associated acidic protein. This gene is expressed in tissues with motile cilia or flagella, including the trachea, lungs, airway brushings, and testes. Mutations in this gene result in primary ciliary dyskinesia-24. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2014]

RSPH1 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 24

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 21-42472629-G-A is Benign according to our data. Variant chr21-42472629-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1678821.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00593 (903/152162) while in subpopulation AFR AF = 0.0206 (856/41502). AF 95% confidence interval is 0.0195. There are 10 homozygotes in GnomAd4. There are 406 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 10 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080860.4. 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
	RSPH1	NM_080860.4	MANE Select	c.*189C>T		3_prime_UTR	Exon 9 of 9	NP_543136.1	Q8WYR4-1
	RSPH1	NM_001286506.2		c.*189C>T		3_prime_UTR	Exon 8 of 8	NP_001273435.1	Q8WYR4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSPH1	ENST00000291536.8	TSL:1 MANE Select	c.*189C>T		3_prime_UTR	Exon 9 of 9	ENSP00000291536.3	Q8WYR4-1
	RSPH1	ENST00000856519.1		c.*189C>T		3_prime_UTR	Exon 8 of 8	ENSP00000526578.1
	RSPH1	ENST00000856518.1		c.*189C>T		3_prime_UTR	Exon 7 of 7	ENSP00000526577.1

Frequencies

GnomAD3 genomes AF: 0.00589 AC: 895 AN: 152044 Hom.: 8 Cov.: 33

Gnomad AFR AF: 0.0205

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00335

GnomAD4 exome AF: 0.000768 AC: 230 AN: 299494 Hom.: 2 Cov.: 3 AF XY: 0.000615 AC XY: 96 AN XY: 155980

African (AFR) AF: 0.0204 AC: 163 AN: 8000

American (AMR) AF: 0.00162 AC: 15 AN: 9246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10024

East Asian (EAS) AF: 0.00 AC: 0 AN: 23604

South Asian (SAS) AF: 0.0000632 AC: 1 AN: 15816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27268

Middle Eastern (MID) AF: 0.00337 AC: 6 AN: 1782

European-Non Finnish (NFE) AF: 0.0000270 AC: 5 AN: 185298

Other (OTH) AF: 0.00217 AC: 40 AN: 18456

GnomAD4 genome AF: 0.00593 AC: 903 AN: 152162 Hom.: 10 Cov.: 33 AF XY: 0.00546 AC XY: 406 AN XY: 74376

African (AFR) AF: 0.0206 AC: 856 AN: 41502

American (AMR) AF: 0.00242 AC: 37 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67996

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.00112 Hom.: 1

Bravo AF: 0.00702

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.0
DANN	Benign	0.67
PhyloP100		0.57
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: rs111759882; hg19: chr21-43892739;