chr18-70004420-C-T

Position:

• chr18-70004420-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_173630.4(RTTN):​c.6596-184G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.851 in 152,126 control chromosomes in the GnomAD database, including 58,012 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.85 (58012 hom., cov: 31)
• Consequence: RTTN NM_173630.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.781

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 18-70004420-C-T is Benign according to our data. Variant chr18-70004420-C-T is described in ClinVar as [Benign]. Clinvar id is 1295478.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RTTN	NM_173630.4	c.6596-184G>A		intron_variant		ENST00000640769.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RTTN	ENST00000640769.2	c.6596-184G>A		intron_variant		2	NM_173630.4	P1

Frequencies

GnomAD3 genomes AF: 0.851 AC: 129315 AN: 152008 Hom.: 57989 Cov.: 31

Gnomad AFR AF: 0.531

Gnomad AMI AF: 0.895

Gnomad AMR AF: 0.926

Gnomad ASJ AF: 0.969

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.971

Gnomad FIN AF: 0.990

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.978

Gnomad OTH AF: 0.881

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

GnomAD4 genome AF: 0.851 AC: 129391 AN: 152126 Hom.: 58012 Cov.: 31 AF XY: 0.855 AC XY: 63576 AN XY: 74386

Gnomad4 AFR AF: 0.532

Gnomad4 AMR AF: 0.927

Gnomad4 ASJ AF: 0.969

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.973

Gnomad4 FIN AF: 0.990

Gnomad4 NFE AF: 0.978

Gnomad4 OTH AF: 0.882

Alfa AF: 0.908 Hom.: 7595

Bravo AF: 0.829

Asia WGS AF: 0.951 AC: 3278 AN: 3452

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	7.2
DANN	Benign	0.35

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: rs10871658; hg19: chr18-67671656;