rs4920112

Variant names:

• chr21-42475614-T-G
• rs4920112
• NM_080860.4:c.877+284A>C

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.877+284A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 145,314 control chromosomes in the GnomAD database, including 1,447 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.13 (1447 hom., cov: 23)
• Consequence: RSPH1 NM_080860.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0510
• 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, 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=-0.87).
• BP6: Variant 21-42475614-T-G is Benign according to our data. Variant chr21-42475614-T-G is described in ClinVar as Benign. ClinVar VariationId is 1282349.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.17 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.877+284A>C		intron	N/A	NP_543136.1	Q8WYR4-1
	RSPH1	NM_001286506.2		c.763+284A>C		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+284A>C		intron	N/A	ENSP00000291536.3	Q8WYR4-1
	RSPH1	ENST00000856519.1		c.805+284A>C		intron	N/A	ENSP00000526578.1
	RSPH1	ENST00000398352.3	TSL:5	c.763+284A>C		intron	N/A	ENSP00000381395.3	Q8WYR4-2

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19001 AN: 145284 Hom.: 1445 Cov.: 23

Gnomad AFR AF: 0.0680

Gnomad AMI AF: 0.0392

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.131 AC: 19006 AN: 145314 Hom.: 1447 Cov.: 23 AF XY: 0.129 AC XY: 9028 AN XY: 70184

African (AFR) AF: 0.0679 AC: 2678 AN: 39434

American (AMR) AF: 0.101 AC: 1442 AN: 14210

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 568 AN: 3426

East Asian (EAS) AF: 0.148 AC: 723 AN: 4884

South Asian (SAS) AF: 0.103 AC: 415 AN: 4040

European-Finnish (FIN) AF: 0.143 AC: 1354 AN: 9444

Middle Eastern (MID) AF: 0.171 AC: 49 AN: 286

European-Non Finnish (NFE) AF: 0.172 AC: 11495 AN: 66766

Other (OTH) AF: 0.128 AC: 247 AN: 1932

Alfa AF: 0.160 Hom.: 448

Bravo AF: 0.123

Asia WGS AF: 0.120 AC: 417 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	-0.87
CADD	Benign	0.55
DANN	Benign	0.44
PhyloP100		-0.051
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: rs4920112; hg19: chr21-43895724;