Genetic Variant ENST00000365328.1:n.-43C>T (chr6-52995577-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000365328.1(7SK):n.-43C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 165,814 control chromosomes in the GnomAD database, including 5,852 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.26 ( 5497 hom., cov: 33)

Exomes 𝑓: 0.22 ( 355 hom. )

Consequence

7SK
ENST00000365328.1 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.78

Publications

10 publications found

Variant links:

Genes affected

7SK (HGNC:):

7SK links:

RN7SK (HGNC:10037): (RNA component of 7SK nuclear ribonucleoprotein)

RN7SK links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RN7SK	NR_001445.2 link	n.-43C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
7SK	ENST00000365328.1 link	n.-43C>T		upstream_gene_variant		6
RN7SK	ENST00000636484.1 link	n.-44C>T		upstream_gene_variant		6

Frequencies

GnomAD3 genomes

AF:

0.262

AC:

39721

AN:

151838

Hom.:

5477

Cov.:

show subpopulations

Gnomad AFR

AF:

0.341

Gnomad AMI

AF:

0.186

Gnomad AMR

AF:

0.219

Gnomad ASJ

AF:

0.314

Gnomad EAS

AF:

0.132

Gnomad SAS

AF:

0.158

Gnomad FIN

AF:

0.207

Gnomad MID

AF:

0.310

Gnomad NFE

AF:

0.247

Gnomad OTH

AF:

0.256

GnomAD4 exome

AF:

0.219

AC:

3029

AN:

13858

Hom.:

355

Cov.:

AF XY:

0.219

AC XY:

1427

AN XY:

6502

show subpopulations

African (AFR)

AF:

0.331

AC:

149

AN:

450

American (AMR)

AF:

0.190

AC:

AN:

268

Ashkenazi Jewish (ASJ)

AF:

0.262

AC:

229

AN:

874

East Asian (EAS)

AF:

0.139

AC:

435

AN:

3124

South Asian (SAS)

AF:

0.113

AC:

AN:

106

European-Finnish (FIN)

AF:

0.224

AC:

AN:

228

Middle Eastern (MID)

AF:

0.337

AC:

AN:

European-Non Finnish (NFE)

AF:

0.239

AC:

1827

AN:

7644

Other (OTH)

AF:

0.228

AC:

244

AN:

1072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

111

222

332

443

554

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.262

AC:

39772

AN:

151956

Hom.:

5497

Cov.:

AF XY:

0.256

AC XY:

19043

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.342

AC:

14174

AN:

41504

American (AMR)

AF:

0.219

AC:

3341

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.314

AC:

1087

AN:

3460

East Asian (EAS)

AF:

0.132

AC:

684

AN:

5174

South Asian (SAS)

AF:

0.157

AC:

756

AN:

4818

European-Finnish (FIN)

AF:

0.207

AC:

2195

AN:

10584

Middle Eastern (MID)

AF:

0.296

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.247

AC:

16744

AN:

67832

Other (OTH)

AF:

0.253

AC:

535

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1502

3004

4505

6007

7509

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

406

812

1218

1624

2030

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.210

Hom.:

1705

Bravo

AF:

0.267

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.0010

(source)

DANN

Benign

0.74

PhyloP100

-5.8

PromoterAI

-0.059

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over