Genetic Variant TOLLIP-DT:n.256G>C (chr11-1310024-G-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000530897.1(TOLLIP-DT):n.256G>C 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 0.817 in 152,320 control chromosomes in the GnomAD database, including 51,411 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.82 ( 51388 hom., cov: 34)

Exomes 𝑓: 0.81 ( 23 hom. )

Consequence

TOLLIP-DT
ENST00000530897.1 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.994

Publications

26 publications found

Variant links:

COSMIC-nc: COSV55136949

Genes affected

TOLLIP-DT (HGNC:27403): (TOLLIP divergent transcript)

TOLLIP-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 11-1310024-G-C is Benign according to our data. Variant chr11-1310024-G-C is described in ClinVar as Benign. ClinVar VariationId is 1249282.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000530897.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOLLIP-DT	NR_029409.1		n.317G>C		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOLLIP-DT	ENST00000530897.1	TSL:6	n.256G>C		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.817

AC:

124269

AN:

152132

Hom.:

51372

Cov.:

show subpopulations

Gnomad AFR

AF:

0.696

Gnomad AMI

AF:

0.825

Gnomad AMR

AF:

0.864

Gnomad ASJ

AF:

0.863

Gnomad EAS

AF:

0.619

Gnomad SAS

AF:

0.792

Gnomad FIN

AF:

0.818

Gnomad MID

AF:

0.820

Gnomad NFE

AF:

0.894

Gnomad OTH

AF:

0.828

GnomAD4 exome

AF:

0.814

AC:

AN:

Hom.:

Cov.:

AF XY:

0.810

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.750

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.833

AC:

AN:

South Asian (SAS)

AF:

0.833

AC:

AN:

European-Finnish (FIN)

AF:

0.750

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.818

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.817

AC:

124327

AN:

152250

Hom.:

51388

Cov.:

AF XY:

0.812

AC XY:

60444

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.696

AC:

28890

AN:

41538

American (AMR)

AF:

0.864

AC:

13227

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.863

AC:

2998

AN:

3472

East Asian (EAS)

AF:

0.618

AC:

3189

AN:

5158

South Asian (SAS)

AF:

0.794

AC:

3835

AN:

4832

European-Finnish (FIN)

AF:

0.818

AC:

8665

AN:

10596

Middle Eastern (MID)

AF:

0.820

AC:

241

AN:

294

European-Non Finnish (NFE)

AF:

0.894

AC:

60783

AN:

68026

Other (OTH)

AF:

0.826

AC:

1748

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1133

2265

3398

4530

5663

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

880

1760

2640

3520

4400

<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:

0.855

Hom.:

6965

Bravo

AF:

0.815

Asia WGS

AF:

0.688

AC:

2391

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Jan 11, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 28463648)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.7

(source)

DANN

Benign

0.64

PhyloP100

-0.99

PromoterAI

0.041

Neutral

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over