NM_080860.4:c.*287A>G

Variant names:

• chr21-42472531-T-C
• rs2839531
• NM_080860.4:c.*287A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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 -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 VariationId 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.

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.*287A>G		3_prime_UTR	Exon 9 of 9	NP_543136.1	Q8WYR4-1
	RSPH1	NM_001286506.2		c.*287A>G		3_prime_UTR	Exon 8 of 8	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.*287A>G		3_prime_UTR	Exon 9 of 9	ENSP00000291536.3	Q8WYR4-1
	RSPH1	ENST00000856519.1		c.*287A>G		3_prime_UTR	Exon 8 of 8	ENSP00000526578.1
	RSPH1	ENST00000856518.1		c.*287A>G		3_prime_UTR	Exon 7 of 7	ENSP00000526577.1

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

African (AFR) AF: 0.809 AC: 2595 AN: 3208

American (AMR) AF: 0.917 AC: 2756 AN: 3006

Ashkenazi Jewish (ASJ) AF: 0.933 AC: 3773 AN: 4046

East Asian (EAS) AF: 0.744 AC: 5753 AN: 7732

South Asian (SAS) AF: 0.967 AC: 2500 AN: 2586

European-Finnish (FIN) AF: 0.947 AC: 4813 AN: 5080

Middle Eastern (MID) AF: 0.915 AC: 465 AN: 508

European-Non Finnish (NFE) AF: 0.940 AC: 60734 AN: 64582

Other (OTH) AF: 0.915 AC: 6232 AN: 6810

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

African (AFR) AF: 0.810 AC: 33634 AN: 41530

American (AMR) AF: 0.899 AC: 13768 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.939 AC: 3260 AN: 3470

East Asian (EAS) AF: 0.744 AC: 3859 AN: 5184

South Asian (SAS) AF: 0.968 AC: 4674 AN: 4828

European-Finnish (FIN) AF: 0.958 AC: 10173 AN: 10620

Middle Eastern (MID) AF: 0.912 AC: 268 AN: 294

European-Non Finnish (NFE) AF: 0.940 AC: 63928 AN: 68026

Other (OTH) AF: 0.904 AC: 1909 AN: 2112

Alfa AF: 0.924 Hom.: 121519

Bravo AF: 0.884

Asia WGS AF: 0.871 AC: 3029 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.5
DANN	Benign	0.76
PhyloP100		0.43
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: rs2839531; hg19: chr21-43892641;