NM_080860.4:c.878-204C>T

Variant names:

• chr21-42473074-G-A
• rs2839532
• NM_080860.4:c.878-204C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_080860.4(RSPH1):​c.878-204C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 152,006 control chromosomes in the GnomAD database, including 8,298 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.32 (8298 hom., cov: 33)
• Consequence: RSPH1 NM_080860.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.627
• Publications: 1 publications found

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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 21-42473074-G-A is Benign according to our data. Variant chr21-42473074-G-A is described in ClinVar as Benign. ClinVar VariationId is 1263479.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

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.878-204C>T		intron	N/A	NP_543136.1	Q8WYR4-1
	RSPH1	NM_001286506.2		c.764-204C>T		intron	N/A	NP_001273435.1	Q8WYR4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSPH1	ENST00000291536.8	TSL:1 MANE Select	c.878-204C>T		intron	N/A	ENSP00000291536.3	Q8WYR4-1
	RSPH1	ENST00000856519.1		c.806-204C>T		intron	N/A	ENSP00000526578.1
	RSPH1	ENST00000398352.3	TSL:5	c.764-204C>T		intron	N/A	ENSP00000381395.3	Q8WYR4-2

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49253 AN: 151888 Hom.: 8305 Cov.: 33

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.326

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

GnomAD4 genome AF: 0.324 AC: 49251 AN: 152006 Hom.: 8298 Cov.: 33 AF XY: 0.327 AC XY: 24281 AN XY: 74290

African (AFR) AF: 0.231 AC: 9585 AN: 41462

American (AMR) AF: 0.305 AC: 4663 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1015 AN: 3466

East Asian (EAS) AF: 0.382 AC: 1976 AN: 5170

South Asian (SAS) AF: 0.346 AC: 1669 AN: 4820

European-Finnish (FIN) AF: 0.405 AC: 4261 AN: 10522

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.368 AC: 25038 AN: 67974

Other (OTH) AF: 0.324 AC: 684 AN: 2110

Alfa AF: 0.327 Hom.: 1204

Bravo AF: 0.313

Asia WGS AF: 0.344 AC: 1197 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.42
DANN	Benign	0.88
PhyloP100		-0.63
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2839532; hg19: chr21-43893184;