21-42475749-C-T

Position:

• chr21-42475749-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_080860.4(RSPH1):​c.877+149G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00362 in 639,842 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (37 hom., cov: 24)
  • Exomes 𝑓: 0.0016 (7 hom.)
• Consequence: RSPH1 NM_080860.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.714

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=-0.89).
• BP6: Variant 21-42475749-C-T is Benign according to our data. Variant chr21-42475749-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1203615.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0123 (1497/121942) while in subpopulation AFR AF= 0.042 (1398/33260). AF 95% confidence interval is 0.0402. There are 37 homozygotes in gnomad4. There are 682 alleles in male gnomad4 subpopulation. Median coverage is 24. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 37 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSPH1	NM_080860.4	c.877+149G>A		intron_variant		ENST00000291536.8	NP_543136.1
RSPH1	NM_001286506.2	c.763+149G>A		intron_variant			NP_001273435.1
RSPH1	XM_005261208.3	c.670+149G>A		intron_variant			XP_005261265.1
RSPH1	XM_011529786.2	c.805+149G>A		intron_variant			XP_011528088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSPH1	ENST00000291536.8	c.877+149G>A		intron_variant		1	NM_080860.4	ENSP00000291536	P1
RSPH1	ENST00000398352.3	c.763+149G>A		intron_variant		5		ENSP00000381395
RSPH1	ENST00000493019.1	n.2495+149G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0122 AC: 1488 AN: 121820 Hom.: 37 Cov.: 24

Gnomad AFR AF: 0.0419

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00697

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000398

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00323

Gnomad NFE AF: 0.000244

Gnomad OTH AF: 0.0107

GnomAD4 exome AF: 0.00159 AC: 821 AN: 517900 Hom.: 7 AF XY: 0.00129 AC XY: 347 AN XY: 268230

Gnomad4 AFR exome AF: 0.0425

Gnomad4 AMR exome AF: 0.00419

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000152

Gnomad4 OTH exome AF: 0.00359

GnomAD4 genome AF: 0.0123 AC: 1497 AN: 121942 Hom.: 37 Cov.: 24 AF XY: 0.0120 AC XY: 682 AN XY: 56832

Gnomad4 AFR AF: 0.0420

Gnomad4 AMR AF: 0.00696

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000399

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000244

Gnomad4 OTH AF: 0.0105

Alfa AF: 0.00902 Hom.: 1

Asia WGS AF: 0.00346 AC: 13 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 13, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.29
DANN	Benign	0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs73374124; hg19: chr21-43895859;