chr21-42475588-G-A

Position:

• chr21-42475588-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_080860.4(RSPH1):​c.877+310C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 143,160 control chromosomes in the GnomAD database, including 3,221 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.20 (3221 hom., cov: 22)
• Consequence: RSPH1 NM_080860.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.62

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 21-42475588-G-A is Benign according to our data. Variant chr21-42475588-G-A is described in ClinVar as [Benign]. Clinvar id is 1250641.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSPH1	NM_080860.4	c.877+310C>T		intron_variant		ENST00000291536.8	NP_543136.1
RSPH1	NM_001286506.2	c.763+310C>T		intron_variant			NP_001273435.1
RSPH1	XM_005261208.3	c.670+310C>T		intron_variant			XP_005261265.1
RSPH1	XM_011529786.2	c.805+310C>T		intron_variant			XP_011528088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSPH1	ENST00000291536.8	c.877+310C>T		intron_variant		1	NM_080860.4	ENSP00000291536	P1
RSPH1	ENST00000398352.3	c.763+310C>T		intron_variant		5		ENSP00000381395
RSPH1	ENST00000493019.1	n.2495+310C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.198 AC: 28268 AN: 143068 Hom.: 3222 Cov.: 22

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.00722

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.165

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.198 AC: 28282 AN: 143160 Hom.: 3221 Cov.: 22 AF XY: 0.193 AC XY: 13310 AN XY: 68978

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.00723

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.197

Gnomad4 OTH AF: 0.163

Alfa AF: 0.206 Hom.: 505

Bravo AF: 0.206

Asia WGS AF: 0.0530 AC: 180 AN: 3366

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.45
DANN	Benign	0.53

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

Other links and lift over

dbSNP: rs114954017; hg19: chr21-43895698; COSMIC: COSV52321270;