chr21-42472665-G-A

Position:

• chr21-42472665-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_080860.4(RSPH1):​c.*153C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 549,068 control chromosomes in the GnomAD database, including 54,439 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (12424 hom., cov: 32)
  • Exomes 𝑓: 0.46 (42015 hom.)
• Consequence: RSPH1 NM_080860.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.74

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 21-42472665-G-A is Benign according to our data. Variant chr21-42472665-G-A is described in ClinVar as [Benign]. Clinvar id is 1274561.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSPH1	NM_080860.4	c.*153C>T		3_prime_UTR_variant	9/9	ENST00000291536.8	NP_543136.1
RSPH1	NM_001286506.2	c.*153C>T		3_prime_UTR_variant	8/8		NP_001273435.1
RSPH1	XM_005261208.3	c.*153C>T		3_prime_UTR_variant	7/7		XP_005261265.1
RSPH1	XM_011529786.2	c.*153C>T		3_prime_UTR_variant	8/8		XP_011528088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSPH1	ENST00000291536.8	c.*153C>T		3_prime_UTR_variant	9/9	1	NM_080860.4	ENSP00000291536	P1
RSPH1	ENST00000493019.1	n.2701C>T		non_coding_transcript_exon_variant	8/8	2
RSPH1	ENST00000398352.3			downstream_gene_variant		5		ENSP00000381395

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58455 AN: 151756 Hom.: 12427 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.426

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.406

GnomAD4 exome AF: 0.455 AC: 180886 AN: 397196 Hom.: 42015 Cov.: 5 AF XY: 0.460 AC XY: 97045 AN XY: 211112

Gnomad4 AFR exome AF: 0.193

Gnomad4 AMR exome AF: 0.358

Gnomad4 ASJ exome AF: 0.411

Gnomad4 EAS exome AF: 0.502

Gnomad4 SAS exome AF: 0.508

Gnomad4 FIN exome AF: 0.480

Gnomad4 NFE exome AF: 0.460

Gnomad4 OTH exome AF: 0.441

GnomAD4 genome AF: 0.385 AC: 58478 AN: 151872 Hom.: 12424 Cov.: 32 AF XY: 0.390 AC XY: 28937 AN XY: 74208

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.388

Gnomad4 ASJ AF: 0.422

Gnomad4 EAS AF: 0.510

Gnomad4 SAS AF: 0.507

Gnomad4 FIN AF: 0.483

Gnomad4 NFE AF: 0.462

Gnomad4 OTH AF: 0.410

Alfa AF: 0.400 Hom.: 1610

Bravo AF: 0.370

Asia WGS AF: 0.488 AC: 1696 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.35
DANN	Benign	0.39

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: rs11203205; hg19: chr21-43892775;