18-70005060-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_173630.4(RTTN):​c.6595+138A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00209 in 520,392 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0052 ( 8 hom., cov: 32)
Exomes 𝑓: 0.00080 ( 2 hom. )

Consequence

RTTN
NM_173630.4 intron

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.152
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 18-70005060-T-C is Benign according to our data. Variant chr18-70005060-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1206839.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0052 (792/152354) while in subpopulation AFR AF= 0.0179 (745/41582). AF 95% confidence interval is 0.0169. There are 8 homozygotes in gnomad4. There are 372 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RTTNNM_173630.4 linkuse as main transcriptc.6595+138A>G intron_variant ENST00000640769.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RTTNENST00000640769.2 linkuse as main transcriptc.6595+138A>G intron_variant 2 NM_173630.4 P1Q86VV8-1

Frequencies

GnomAD3 genomes
AF:
0.00521
AC:
793
AN:
152236
Hom.:
8
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0180
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00183
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00525
GnomAD4 exome
AF:
0.000804
AC:
296
AN:
368038
Hom.:
2
AF XY:
0.000695
AC XY:
133
AN XY:
191330
show subpopulations
Gnomad4 AFR exome
AF:
0.0210
Gnomad4 AMR exome
AF:
0.00269
Gnomad4 ASJ exome
AF:
0.0000855
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000835
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000101
Gnomad4 OTH exome
AF:
0.00138
GnomAD4 genome
AF:
0.00520
AC:
792
AN:
152354
Hom.:
8
Cov.:
32
AF XY:
0.00499
AC XY:
372
AN XY:
74510
show subpopulations
Gnomad4 AFR
AF:
0.0179
Gnomad4 AMR
AF:
0.00183
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00520
Alfa
AF:
0.00354
Hom.:
0
Bravo
AF:
0.00562
Asia WGS
AF:
0.00116
AC:
4
AN:
3474

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxAug 17, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
5.2
DANN
Benign
0.80

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs115029214; hg19: chr18-67672296; API