Variant 21-42475786-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_080860.4(RSPH1):c.877+112G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0569 in 1,257,322 control chromosomes in the GnomAD database, including 2,279 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.049 ( 174 hom., cov: 25)

Exomes 𝑓: 0.058 ( 2105 hom. )

Consequence

RSPH1
NM_080860.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.05

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 -14 ACMG points.

BP4

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

BP6

Variant 21-42475786-C-T is Benign according to our data. Variant chr21-42475786-C-T is described in ClinVar as [Benign]. Clinvar id is 1271573.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
RSPH1	NM_080860.4 linkuse as main transcript	c.877+112G>A	intron_variant	ENST00000291536.8	NP_543136.1
RSPH1	NM_001286506.2 linkuse as main transcript	c.763+112G>A	intron_variant		NP_001273435.1
RSPH1	XM_005261208.3 linkuse as main transcript	c.670+112G>A	intron_variant		XP_005261265.1
RSPH1	XM_011529786.2 linkuse as main transcript	c.805+112G>A	intron_variant		XP_011528088.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
RSPH1	ENST00000291536.8 linkuse as main transcript	c.877+112G>A	intron_variant	1	NM_080860.4	ENSP00000291536	P1	Q8WYR4-1
RSPH1	ENST00000398352.3 linkuse as main transcript	c.763+112G>A	intron_variant	5		ENSP00000381395		Q8WYR4-2
RSPH1	ENST00000493019.1 linkuse as main transcript	n.2495+112G>A	intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.0486

AC:

6203

AN:

127564

Hom.:

172

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0339

Gnomad AMI

AF:

0.0331

Gnomad AMR

AF:

0.0377

Gnomad ASJ

AF:

0.101

Gnomad EAS

AF:

0.000665

Gnomad SAS

AF:

0.0135

Gnomad FIN

AF:

0.0501

Gnomad MID

AF:

0.0948

Gnomad NFE

AF:

0.0610

Gnomad OTH

AF:

0.0560

GnomAD4 exome

AF:

0.0578

AC:

65298

AN:

1129634

Hom.:

2105

AF XY:

0.0573

AC XY:

32353

AN XY:

564798

show subpopulations

Gnomad4 AFR exome

AF:

0.0360

Gnomad4 AMR exome

AF:

0.0330

Gnomad4 ASJ exome

AF:

0.104

Gnomad4 EAS exome

AF:

0.000134

Gnomad4 SAS exome

AF:

0.0251

Gnomad4 FIN exome

AF:

0.0561

Gnomad4 NFE exome

AF:

0.0634

Gnomad4 OTH exome

AF:

0.0585

GnomAD4 genome

AF:

0.0487

AC:

6218

AN:

127688

Hom.:

174

Cov.:

AF XY:

0.0474

AC XY:

2848

AN XY:

60078

show subpopulations

Gnomad4 AFR

AF:

0.0343

Gnomad4 AMR

AF:

0.0375

Gnomad4 ASJ

AF:

0.101

Gnomad4 EAS

AF:

0.000666

Gnomad4 SAS

AF:

0.0139

Gnomad4 FIN

AF:

0.0501

Gnomad4 NFE

AF:

0.0610

Gnomad4 OTH

AF:

0.0551

Alfa

AF:

0.0510

Hom.:

Bravo

AF:

0.0484

Asia WGS

AF:

0.0100

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 28, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.35

DANN

Benign

0.40

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