chr21-42472531-T-C

Position:

• chr21-42472531-T-C

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.*287A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.904 in 249,842 control chromosomes in the GnomAD database, including 102,735 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.90 (61378 hom., cov: 33)
  • Exomes 𝑓: 0.92 (41357 hom.)
• Consequence: RSPH1 NM_080860.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.434

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=-0.91).
• BP6: Variant 21-42472531-T-C is Benign according to our data. Variant chr21-42472531-T-C is described in ClinVar as [Benign]. Clinvar id is 1179831.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSPH1	NM_080860.4	c.*287A>G		3_prime_UTR_variant	9/9	ENST00000291536.8	NP_543136.1
RSPH1	NM_001286506.2	c.*287A>G		3_prime_UTR_variant	8/8		NP_001273435.1
RSPH1	XM_005261208.3	c.*287A>G		3_prime_UTR_variant	7/7		XP_005261265.1
RSPH1	XM_011529786.2	c.*287A>G		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.*287A>G		3_prime_UTR_variant	9/9	1	NM_080860.4	ENSP00000291536	P1
RSPH1	ENST00000493019.1	n.2835A>G		non_coding_transcript_exon_variant	8/8	2

Frequencies

GnomAD3 genomes AF: 0.895 AC: 136213 AN: 152166 Hom.: 61330 Cov.: 33

Gnomad AFR AF: 0.810

Gnomad AMI AF: 0.925

Gnomad AMR AF: 0.899

Gnomad ASJ AF: 0.939

Gnomad EAS AF: 0.745

Gnomad SAS AF: 0.968

Gnomad FIN AF: 0.958

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.940

Gnomad OTH AF: 0.903

GnomAD4 exome AF: 0.919 AC: 89621 AN: 97558 Hom.: 41357 Cov.: 0 AF XY: 0.923 AC XY: 45697 AN XY: 49516

Gnomad4 AFR exome AF: 0.809

Gnomad4 AMR exome AF: 0.917

Gnomad4 ASJ exome AF: 0.933

Gnomad4 EAS exome AF: 0.744

Gnomad4 SAS exome AF: 0.967

Gnomad4 FIN exome AF: 0.947

Gnomad4 NFE exome AF: 0.940

Gnomad4 OTH exome AF: 0.915

GnomAD4 genome AF: 0.895 AC: 136317 AN: 152284 Hom.: 61378 Cov.: 33 AF XY: 0.897 AC XY: 66759 AN XY: 74464

Gnomad4 AFR AF: 0.810

Gnomad4 AMR AF: 0.899

Gnomad4 ASJ AF: 0.939

Gnomad4 EAS AF: 0.744

Gnomad4 SAS AF: 0.968

Gnomad4 FIN AF: 0.958

Gnomad4 NFE AF: 0.940

Gnomad4 OTH AF: 0.904

Alfa AF: 0.930 Hom.: 83695

Bravo AF: 0.884

Asia WGS AF: 0.871 AC: 3029 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 27, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.5
DANN	Benign	0.76

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: rs2839531; hg19: chr21-43892641;