12-6943867-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NR_023317.1(RNU7-1):​n.52C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0181 in 939,128 control chromosomes in the GnomAD database, including 186 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 20 hom., cov: 33)
Exomes 𝑓: 0.019 ( 166 hom. )

Consequence

RNU7-1
NR_023317.1 non_coding_transcript_exon

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.752
Variant links:
Genes affected
RNU7-1 (HGNC:34033): (RNA, U7 small nuclear 1) Implicated in Aicardi-Goutieres syndrome. [provided by Alliance of Genome Resources, Apr 2022]
C12orf57 (HGNC:29521): (chromosome 12 open reading frame 57) This gene is ubiquitously expressed in human tissues. It is required for development of the human corpus callosum. Mutations in this gene are associated with Temtamy syndrome (TEMTYS). Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2014]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.62).
BP6
Variant 12-6943867-C-T is Benign according to our data. Variant chr12-6943867-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1301050.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0154 (2344/152260) while in subpopulation AMR AF= 0.0223 (341/15294). AF 95% confidence interval is 0.0203. There are 20 homozygotes in gnomad4. There are 1077 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 20 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RNU7-1NR_023317.1 linkuse as main transcriptn.52C>T non_coding_transcript_exon_variant 1/1
C12orf57NM_001301834.1 linkuse as main transcriptc.-16+205C>T intron_variant
C12orf57NM_001301836.2 linkuse as main transcriptc.13+205C>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RNU7-1ENST00000458811.1 linkuse as main transcriptn.52C>T non_coding_transcript_exon_variant 1/1
ENST00000607421.2 linkuse as main transcriptn.764G>A non_coding_transcript_exon_variant 1/1

Frequencies

GnomAD3 genomes
AF:
0.0154
AC:
2343
AN:
152142
Hom.:
20
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00956
Gnomad AMI
AF:
0.0329
Gnomad AMR
AF:
0.0223
Gnomad ASJ
AF:
0.0334
Gnomad EAS
AF:
0.00116
Gnomad SAS
AF:
0.00643
Gnomad FIN
AF:
0.00755
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0191
Gnomad OTH
AF:
0.0211
GnomAD4 exome
AF:
0.0186
AC:
14674
AN:
786868
Hom.:
166
Cov.:
10
AF XY:
0.0187
AC XY:
7373
AN XY:
394480
show subpopulations
Gnomad4 AFR exome
AF:
0.00838
Gnomad4 AMR exome
AF:
0.0228
Gnomad4 ASJ exome
AF:
0.0299
Gnomad4 EAS exome
AF:
0.000931
Gnomad4 SAS exome
AF:
0.00909
Gnomad4 FIN exome
AF:
0.00767
Gnomad4 NFE exome
AF:
0.0208
Gnomad4 OTH exome
AF:
0.0170
GnomAD4 genome
AF:
0.0154
AC:
2344
AN:
152260
Hom.:
20
Cov.:
33
AF XY:
0.0145
AC XY:
1077
AN XY:
74440
show subpopulations
Gnomad4 AFR
AF:
0.00953
Gnomad4 AMR
AF:
0.0223
Gnomad4 ASJ
AF:
0.0334
Gnomad4 EAS
AF:
0.00116
Gnomad4 SAS
AF:
0.00644
Gnomad4 FIN
AF:
0.00755
Gnomad4 NFE
AF:
0.0191
Gnomad4 OTH
AF:
0.0213
Alfa
AF:
0.00429
Hom.:
0
Bravo
AF:
0.0164

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Likely benign, criteria provided, single submitterclinical testingGeneDxMar 29, 2021- -
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.62
CADD
Benign
0.058
DANN
Benign
0.72
RBP_binding_hub_radar
1.1
RBP_regulation_power_radar
2.3

Splicing

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: rs149374821; hg19: chr12-7053030; API