rs4820539

Positions:

• chr22-23135783-A-G
• chr22-23135783-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014433.3(RSPH14):​c.303-1639T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 151,640 control chromosomes in the GnomAD database, including 25,246 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.57 (25246 hom., cov: 30)
• Consequence: RSPH14 NM_014433.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.87

Genes affected

RSPH14 (HGNC:13437): (radial spoke head 14 homolog) This gene encodes a protein with no known function but with slight similarity to a yeast vacuolar protein. The gene is located in a region deleted in pediatric rhabdoid tumors of the brain, kidney and soft tissues, but mutations in this gene have not been associated with the disease. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSPH14	NM_014433.3	c.303-1639T>C		intron_variant		ENST00000216036.9	NP_055248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSPH14	ENST00000216036.9	c.303-1639T>C		intron_variant		1	NM_014433.3	ENSP00000216036	P1
RSPH14	ENST00000439064.1	c.76-1639T>C		intron_variant		3		ENSP00000406822

Frequencies

GnomAD3 genomes AF: 0.573 AC: 86800 AN: 151526 Hom.: 25231 Cov.: 30

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.580

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.580

Gnomad NFE AF: 0.562

Gnomad OTH AF: 0.557

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

GnomAD4 genome AF: 0.573 AC: 86864 AN: 151640 Hom.: 25246 Cov.: 30 AF XY: 0.567 AC XY: 42041 AN XY: 74104

Gnomad4 AFR AF: 0.652

Gnomad4 AMR AF: 0.556

Gnomad4 ASJ AF: 0.556

Gnomad4 EAS AF: 0.392

Gnomad4 SAS AF: 0.440

Gnomad4 FIN AF: 0.511

Gnomad4 NFE AF: 0.562

Gnomad4 OTH AF: 0.553

Alfa AF: 0.540 Hom.: 9804

Bravo AF: 0.581

Asia WGS AF: 0.434 AC: 1508 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.096
DANN	Benign	0.53

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: rs4820539; hg19: chr22-23477970;