Variant chr21-42485720-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_080860.4(RSPH1):c.450C>T(p.Ala150=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 1,614,138 control chromosomes in the GnomAD database, including 116 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0060 ( 10 hom., cov: 33)

Exomes 𝑓: 0.011 ( 106 hom. )

Consequence

RSPH1
NM_080860.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.859

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 21-42485720-G-A is Benign according to our data. Variant chr21-42485720-G-A is described in ClinVar as [Benign]. Clinvar id is 241784.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.859 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00596 (908/152266) while in subpopulation NFE AF= 0.0105 (713/68022). AF 95% confidence interval is 0.00984. There are 10 homozygotes in gnomad4. There are 437 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RSPH1	NM_080860.4 linkuse as main transcript	c.450C>T	p.Ala150=	synonymous_variant	5/9	ENST00000291536.8
RSPH1	NM_001286506.2 linkuse as main transcript	c.336C>T	p.Ala112=	synonymous_variant	4/8
RSPH1	XM_011529786.2 linkuse as main transcript	c.450C>T	p.Ala150=	synonymous_variant	5/8
RSPH1	XM_005261208.3 linkuse as main transcript	c.243C>T	p.Ala81=	synonymous_variant	3/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RSPH1	ENST00000291536.8 linkuse as main transcript	c.450C>T	p.Ala150=	synonymous_variant	5/9	1	NM_080860.4	P1	Q8WYR4-1
RSPH1	ENST00000398352.3 linkuse as main transcript	c.336C>T	p.Ala112=	synonymous_variant	4/8	5			Q8WYR4-2
RSPH1	ENST00000493019.1 linkuse as main transcript	n.1076C>T		non_coding_transcript_exon_variant	4/8	2

Frequencies

GnomAD3 genomes

AF:

0.00596

AC:

907

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00205

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00801

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0105

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00605

AC:

1522

AN:

251486

Hom.:

AF XY:

0.00614

AC XY:

834

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.00191

Gnomad AMR exome

AF:

0.000954

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.00850

Gnomad NFE exome

AF:

0.0108

Gnomad OTH exome

AF:

0.00587

GnomAD4 exome

AF:

0.0108

AC:

15717

AN:

1461872

Hom.:

106

Cov.:

AF XY:

0.0104

AC XY:

7535

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00161

Gnomad4 AMR exome

AF:

0.00107

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000556

Gnomad4 FIN exome

AF:

0.00910

Gnomad4 NFE exome

AF:

0.0132

Gnomad4 OTH exome

AF:

0.00707

GnomAD4 genome

AF:

0.00596

AC:

908

AN:

152266

Hom.:

Cov.:

AF XY:

0.00587

AC XY:

437

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00205

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000623

Gnomad4 FIN

AF:

0.00801

Gnomad4 NFE

AF:

0.0105

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00980

Hom.:

Bravo

AF:

0.00537

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0105

EpiControl

AF:

0.00907

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

2.1

DANN

Benign

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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