rs1369290

Positions:

• chr18-70024284-A-C
• chr18-70024284-A-T

Variant summary

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

The NM_173630.4(RTTN):​c.5950+438T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 152,190 control chromosomes in the GnomAD database, including 51,365 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 0.76 (51365 hom., cov: 32)
• Consequence: RTTN NM_173630.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.224

Genes affected

RTTN (HGNC:18654): (rotatin) This gene encodes a large protein whose specific function is unknown. Absence of the orthologous protein in mouse results in embryonic lethality with deficient axial rotation, abnormal differentiation of the neural tube, and randomized looping of the heart tube during development. In human, mutations in this gene are associated with polymicrogyria with seizures. In human fibroblasts this protein localizes at the ciliary basal bodies. Given the intracellular localization of this protein and the phenotypic effects of mutations, this gene is suspected of playing a role in the maintenance of normal ciliary structure which in turn effects the developmental process of left-right organ specification, axial rotation, and perhaps notochord development. [provided by RefSeq, Jan 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTTN	NM_173630.4	c.5950+438T>G		intron_variant		ENST00000640769.2	NP_775901.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RTTN	ENST00000640769.2	c.5950+438T>G		intron_variant		2	NM_173630.4	ENSP00000491507.1

Frequencies

GnomAD3 genomes AF: 0.760 AC: 115615 AN: 152072 Hom.: 51360 Cov.: 32

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.888

Gnomad AMR AF: 0.892

Gnomad ASJ AF: 0.956

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.932

Gnomad FIN AF: 0.972

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.958

Gnomad OTH AF: 0.813

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

GnomAD4 genome AF: 0.760 AC: 115631 AN: 152190 Hom.: 51365 Cov.: 32 AF XY: 0.767 AC XY: 57084 AN XY: 74398

Gnomad4 AFR AF: 0.259

Gnomad4 AMR AF: 0.892

Gnomad4 ASJ AF: 0.956

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.932

Gnomad4 FIN AF: 0.972

Gnomad4 NFE AF: 0.958

Gnomad4 OTH AF: 0.815

Alfa AF: 0.813 Hom.: 8338

Bravo AF: 0.731

Asia WGS AF: 0.909 AC: 3159 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.5
DANN	Benign	0.47

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: rs1369290; hg19: chr18-67691520;