rs7275527

Variant names:

• chr21-42475587-T-A
• rs7275527
• NM_080860.4:c.877+311A>T

Your query was ambiguous. Multiple possible variants found:

• chr21-42475587-T-A
• chr21-42475587-T-C
• chr21-42475587-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_080860.4(RSPH1):​c.877+311A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000706 in 141,544 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000071 (0 hom., cov: 22)
• Consequence: RSPH1 NM_080860.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.46
• Publications: 0 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, PanelApp Australia, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).

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+311A>T		intron	N/A	NP_543136.1	Q8WYR4-1
	RSPH1	NM_001286506.2		c.763+311A>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.877+311A>T		intron	N/A	ENSP00000291536.3	Q8WYR4-1
	RSPH1	ENST00000856519.1		c.805+311A>T		intron	N/A	ENSP00000526578.1
	RSPH1	ENST00000398352.3	TSL:5	c.763+311A>T		intron	N/A	ENSP00000381395.3	Q8WYR4-2

Frequencies

GnomAD3 genomes AF: 0.00000706 AC: 1 AN: 141544 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.0000266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.00000706 AC: 1 AN: 141544 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 67942

African (AFR) AF: 0.0000266 AC: 1 AN: 37602

American (AMR) AF: 0.00 AC: 0 AN: 13868

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3404

East Asian (EAS) AF: 0.00 AC: 0 AN: 4916

South Asian (SAS) AF: 0.00 AC: 0 AN: 4084

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66052

Other (OTH) AF: 0.00 AC: 0 AN: 1858

Alfa AF: 0.00 Hom.: 9

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.027
DANN	Benign	0.70
PhyloP100		-3.5

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: rs7275527; hg19: chr21-43895697;