chr18-70004058-C-T

Variant names:

• chr18-70004058-C-T
• rs7998
• NM_173630.4:c.*93G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_173630.4(RTTN):​c.*93G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0805 in 871,694 control chromosomes in the GnomAD database, including 3,151 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.069 (464 hom., cov: 31)
  • Exomes 𝑓: 0.083 (2687 hom.)
• Consequence: RTTN NM_173630.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.78

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP6: Variant 18-70004058-C-T is Benign according to our data. Variant chr18-70004058-C-T is described in ClinVar as [Benign]. Clinvar id is 1221909.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RTTN	NM_173630.4	c.*93G>A		3_prime_UTR_variant	Exon 49 of 49	ENST00000640769.2	NP_775901.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RTTN	ENST00000640769	c.*93G>A		3_prime_UTR_variant	Exon 49 of 49	2	NM_173630.4	ENSP00000491507.1

Frequencies

GnomAD3 genomes AF: 0.0687 AC: 10454 AN: 152106 Hom.: 464 Cov.: 31

Gnomad AFR AF: 0.0176

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.0669

Gnomad ASJ AF: 0.0726

Gnomad EAS AF: 0.0869

Gnomad SAS AF: 0.0851

Gnomad FIN AF: 0.0644

Gnomad MID AF: 0.0382

Gnomad NFE AF: 0.0975

Gnomad OTH AF: 0.0695

GnomAD4 exome AF: 0.0831 AC: 59755 AN: 719470 Hom.: 2687 Cov.: 9 AF XY: 0.0844 AC XY: 32219 AN XY: 381932

Gnomad4 AFR exome AF: 0.0159 AC: 299 AN: 18818

Gnomad4 AMR exome AF: 0.0429 AC: 1702 AN: 39712

Gnomad4 ASJ exome AF: 0.0737 AC: 1468 AN: 19908

Gnomad4 EAS exome AF: 0.0681 AC: 2400 AN: 35250

Gnomad4 SAS exome AF: 0.0790 AC: 5153 AN: 65190

Gnomad4 FIN exome AF: 0.0686 AC: 3259 AN: 47506

Gnomad4 NFE exome AF: 0.0932 AC: 42250 AN: 453448

Gnomad4 Remaining exome AF: 0.0815 AC: 2885 AN: 35420

GnomAD4 genome AF: 0.0687 AC: 10455 AN: 152224 Hom.: 464 Cov.: 31 AF XY: 0.0681 AC XY: 5071 AN XY: 74428

Gnomad4 AFR AF: 0.0175 AC: 0.0175236 AN: 0.0175236

Gnomad4 AMR AF: 0.0668 AC: 0.0667931 AN: 0.0667931

Gnomad4 ASJ AF: 0.0726 AC: 0.0725806 AN: 0.0725806

Gnomad4 EAS AF: 0.0867 AC: 0.0867465 AN: 0.0867465

Gnomad4 SAS AF: 0.0856 AC: 0.0855781 AN: 0.0855781

Gnomad4 FIN AF: 0.0644 AC: 0.0643882 AN: 0.0643882

Gnomad4 NFE AF: 0.0976 AC: 0.0975653 AN: 0.0975653

Gnomad4 OTH AF: 0.0688 AC: 0.0687856 AN: 0.0687856

Alfa AF: 0.0855 Hom.: 759

Bravo AF: 0.0636

Asia WGS AF: 0.0680 AC: 237 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.033
DANN	Benign	0.66
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

Publications

LitVar

Other links and lift over

dbSNP: rs7998; hg19: chr18-67671294; COSMIC: COSV55343661; COSMIC: COSV55343661;