dbSNP rs116369489: RSPH1:c.877+7T>A (chr21-42475891-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_080860.4(RSPH1):c.877+7T>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000134 in 1,594,758 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00075 ( 0 hom., cov: 27)

Exomes 𝑓: 0.000072 ( 1 hom. )

Consequence

RSPH1
NM_080860.4 splice_region, intron

Scores

Splicing: ADA: 0.00001467

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.548

Publications

0 publications found

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 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

RSPH1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 21-42475891-A-T is Benign according to our data. Variant chr21-42475891-A-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 698289.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.877+7T>A		splice_region intron	N/A	NP_543136.1	Q8WYR4-1
	RSPH1	NM_001286506.2		c.763+7T>A		splice_region intron	N/A	NP_001273435.1	Q8WYR4-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RSPH1	ENST00000291536.8	TSL:1 MANE Select	c.877+7T>A	splice_region intron	N/A	ENSP00000291536.3	Q8WYR4-1
RSPH1	ENST00000856519.1		c.805+7T>A	splice_region intron	N/A	ENSP00000526578.1
RSPH1	ENST00000398352.3	TSL:5	c.763+7T>A	splice_region intron	N/A	ENSP00000381395.3	Q8WYR4-2

Frequencies

GnomAD3 genomes

AF:

0.000746

AC:

109

AN:

146068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00272

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000698

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000199

AC:

AN:

251352

AF XY:

0.000133

show subpopulations

Gnomad AFR exome

AF:

0.00295

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000725

AC:

105

AN:

1448572

Hom.:

Cov.:

AF XY:

0.0000624

AC XY:

AN XY:

721334

show subpopulations

African (AFR)

AF:

0.00292

AC:

AN:

33190

American (AMR)

AF:

0.0000224

AC:

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26050

East Asian (EAS)

AF:

0.00

AC:

AN:

39608

South Asian (SAS)

AF:

0.00

AC:

AN:

86028

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53268

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5722

European-Non Finnish (NFE)

AF:

9.09e-7

AC:

AN:

1100042

Other (OTH)

AF:

0.000100

AC:

AN:

59974

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000746

AC:

109

AN:

146186

Hom.:

Cov.:

AF XY:

0.000719

AC XY:

AN XY:

70884

show subpopulations

African (AFR)

AF:

0.00271

AC:

107

AN:

39520

American (AMR)

AF:

0.0000697

AC:

AN:

14344

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3440

East Asian (EAS)

AF:

0.00

AC:

AN:

4818

South Asian (SAS)

AF:

0.00

AC:

AN:

4072

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10116

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66712

Other (OTH)

AF:

0.00

AC:

AN:

1970

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000281

Hom.:

Bravo

AF:

0.000854

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Primary ciliary dyskinesia (1)

Primary ciliary dyskinesia 24 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.19

(source)

DANN

Benign

0.40

PhyloP100

-0.55

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000015

dbscSNV1_RF

Benign

0.0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over