Variant 12-6943875-C-T details in Genebe, Genetics Data Aggregator

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.60C>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 0.00578 in 974,422 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0088 ( 7 hom., cov: 33)

Exomes 𝑓: 0.0052 ( 24 hom. )

Consequence

RNU7-1
NR_023317.1 non_coding_transcript_exon

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.51

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]

RNU7-1 links:

(HGNC:):

links:

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]

C12orf57 links:

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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=-0.48).

BP6

Variant 12-6943875-C-T is Benign according to our data. Variant chr12-6943875-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1301145.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00876 (1334/152252) while in subpopulation AFR AF= 0.018 (747/41552). AF 95% confidence interval is 0.0169. There are 7 homozygotes in gnomad4. There are 620 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons
RNU7-1	NR_023317.1 linkuse as main transcript	n.60C>T	non_coding_transcript_exon_variant	1/1
C12orf57	NM_001301834.1 linkuse as main transcript	c.-16+213C>T	intron_variant
C12orf57	NM_001301836.2 linkuse as main transcript	c.13+213C>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNU7-1	ENST00000458811.1 linkuse as main transcript	n.60C>T		non_coding_transcript_exon_variant	1/1
	ENST00000607421.2 linkuse as main transcript	n.756G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.00876

AC:

1333

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0180

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00589

Gnomad ASJ

AF:

0.00721

Gnomad EAS

AF:

0.00654

Gnomad SAS

AF:

0.00746

Gnomad FIN

AF:

0.000943

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00550

Gnomad OTH

AF:

0.00814

GnomAD4 exome

AF:

0.00523

AC:

4302

AN:

822170

Hom.:

Cov.:

AF XY:

0.00531

AC XY:

2186

AN XY:

411622

show subpopulations

Gnomad4 AFR exome

AF:

0.0166

Gnomad4 AMR exome

AF:

0.00461

Gnomad4 ASJ exome

AF:

0.00633

Gnomad4 EAS exome

AF:

0.00645

Gnomad4 SAS exome

AF:

0.00732

Gnomad4 FIN exome

AF:

0.00119

Gnomad4 NFE exome

AF:

0.00479

Gnomad4 OTH exome

AF:

0.00578

GnomAD4 genome

AF:

0.00876

AC:

1334

AN:

152252

Hom.:

Cov.:

AF XY:

0.00833

AC XY:

620

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0180

Gnomad4 AMR

AF:

0.00588

Gnomad4 ASJ

AF:

0.00721

Gnomad4 EAS

AF:

0.00656

Gnomad4 SAS

AF:

0.00746

Gnomad4 FIN

AF:

0.000943

Gnomad4 NFE

AF:

0.00550

Gnomad4 OTH

AF:

0.00806

Alfa

AF:

0.00414

Hom.:

Bravo

AF:

0.00976

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 submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 02, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over