Variant chr21-42472636-C-T 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_080860.4(RSPH1):c.*182G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0906 in 477,058 control chromosomes in the GnomAD database, including 2,448 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.075 ( 649 hom., cov: 33)

Exomes 𝑓: 0.098 ( 1799 hom. )

Consequence

RSPH1
NM_080860.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.305

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 21-42472636-C-T is Benign according to our data. Variant chr21-42472636-C-T is described in ClinVar as [Benign]. Clinvar id is 1271567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
RSPH1	NM_080860.4 linkuse as main transcript	c.*182G>A	3_prime_UTR_variant	9/9	ENST00000291536.8	NP_543136.1
RSPH1	NM_001286506.2 linkuse as main transcript	c.*182G>A	3_prime_UTR_variant	8/8		NP_001273435.1
RSPH1	XM_005261208.3 linkuse as main transcript	c.*182G>A	3_prime_UTR_variant	7/7		XP_005261265.1
RSPH1	XM_011529786.2 linkuse as main transcript	c.*182G>A	3_prime_UTR_variant	8/8		XP_011528088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSPH1	ENST00000291536.8 linkuse as main transcript	c.*182G>A		3_prime_UTR_variant	9/9	1	NM_080860.4	ENSP00000291536	P1	Q8WYR4-1
RSPH1	ENST00000493019.1 linkuse as main transcript	n.2730G>A		non_coding_transcript_exon_variant	8/8	2

Frequencies

GnomAD3 genomes

AF:

0.0753

AC:

11453

AN:

152176

Hom.:

647

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0185

Gnomad AMI

AF:

0.156

Gnomad AMR

AF:

0.0871

Gnomad ASJ

AF:

0.129

Gnomad EAS

AF:

0.113

Gnomad SAS

AF:

0.158

Gnomad FIN

AF:

0.0780

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.0933

Gnomad OTH

AF:

0.0895

GnomAD4 exome

AF:

0.0979

AC:

31782

AN:

324764

Hom.:

1799

Cov.:

AF XY:

0.100

AC XY:

17046

AN XY:

169802

show subpopulations

Gnomad4 AFR exome

AF:

0.0210

Gnomad4 AMR exome

AF:

0.0777

Gnomad4 ASJ exome

AF:

0.120

Gnomad4 EAS exome

AF:

0.132

Gnomad4 SAS exome

AF:

0.150

Gnomad4 FIN exome

AF:

0.0719

Gnomad4 NFE exome

AF:

0.0948

Gnomad4 OTH exome

AF:

0.0974

GnomAD4 genome

AF:

0.0753

AC:

11463

AN:

152294

Hom.:

649

Cov.:

AF XY:

0.0763

AC XY:

5681

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0184

Gnomad4 AMR

AF:

0.0873

Gnomad4 ASJ

AF:

0.129

Gnomad4 EAS

AF:

0.113

Gnomad4 SAS

AF:

0.158

Gnomad4 FIN

AF:

0.0780

Gnomad4 NFE

AF:

0.0933

Gnomad4 OTH

AF:

0.0956

Alfa

AF:

0.0795

Hom.:

Bravo

AF:

0.0740

Asia WGS

AF:

0.141

AC:

490

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 15, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.7

DANN

Benign

0.53

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