Genetic Variant NM_145206.4:c.*1611C>T (chr10-112816994-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 NM_145206.4(VTI1A):c.*1611C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 231,462 control chromosomes in the GnomAD database, including 8,038 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 0.23 ( 4629 hom., cov: 32)

Exomes 𝑓: 0.28 ( 3409 hom. )

Consequence

VTI1A
NM_145206.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0480

Publications

7 publications found

Variant links:

Genes affected

VTI1A (HGNC:17792): (vesicle transport through interaction with t-SNAREs 1A) The protein encoded by this gene is a member of the family of soluble N-ethylmaleimide-sensitive fusion protein-attachment protein receptors (SNAREs) that function in intracellular trafficking. This family member is involved in vesicular transport between endosomes and the trans-Golgi network. It is a vesicle-associated SNARE (v-SNARE) that interacts with target membrane SNAREs (t-SNAREs). Polymorphisms in this gene have been associated with binocular function, and also with susceptibility to colorectal and lung cancers. A recurrent rearrangement has been found between this gene and the transcription factor 7-like 2 (TCF7L2) gene in colorectal cancers. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

VTI1A links:

ENSG00000285676 (HGNC:):

ENSG00000285676 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=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VTI1A	NM_145206.4 link	c.*1611C>T		3_prime_UTR_variant	Exon 8 of 8	ENST00000393077.3	NP_660207.2	Q96AJ9-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VTI1A	ENST00000393077.3 link	c.*1611C>T		3_prime_UTR_variant	Exon 8 of 8	2	NM_145206.4	ENSP00000376792.2		Q96AJ9-2

Frequencies

GnomAD3 genomes

AF:

0.225

AC:

34201

AN:

151862

Hom.:

4628

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0984

Gnomad AMI

AF:

0.196

Gnomad AMR

AF:

0.243

Gnomad ASJ

AF:

0.242

Gnomad EAS

AF:

0.519

Gnomad SAS

AF:

0.453

Gnomad FIN

AF:

0.209

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.262

Gnomad OTH

AF:

0.218

GnomAD4 exome

AF:

0.277

AC:

22013

AN:

79482

Hom.:

3409

Cov.:

AF XY:

0.279

AC XY:

10202

AN XY:

36558

show subpopulations

African (AFR)

AF:

0.0946

AC:

362

AN:

3826

American (AMR)

AF:

0.237

AC:

582

AN:

2452

Ashkenazi Jewish (ASJ)

AF:

0.237

AC:

1191

AN:

5034

East Asian (EAS)

AF:

0.457

AC:

5103

AN:

11176

South Asian (SAS)

AF:

0.448

AC:

308

AN:

688

European-Finnish (FIN)

AF:

0.197

AC:

AN:

Middle Eastern (MID)

AF:

0.209

AC:

102

AN:

488

European-Non Finnish (NFE)

AF:

0.258

AC:

12665

AN:

49102

Other (OTH)

AF:

0.254

AC:

1687

AN:

6650

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

765

1530

2294

3059

3824

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

168

252

336

420

<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:

0.225

AC:

34211

AN:

151980

Hom.:

4629

Cov.:

AF XY:

0.229

AC XY:

17003

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.0984

AC:

4075

AN:

41426

American (AMR)

AF:

0.243

AC:

3720

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.242

AC:

839

AN:

3468

East Asian (EAS)

AF:

0.518

AC:

2674

AN:

5158

South Asian (SAS)

AF:

0.452

AC:

2175

AN:

4816

European-Finnish (FIN)

AF:

0.209

AC:

2209

AN:

10558

Middle Eastern (MID)

AF:

0.235

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.262

AC:

17804

AN:

67962

Other (OTH)

AF:

0.222

AC:

467

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1297

2595

3892

5190

6487

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

384

768

1152

1536

1920

<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:

0.251

Hom.:

8235

Bravo

AF:

0.218

Asia WGS

AF:

0.454

AC:

1578

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.2

(source)

DANN

Benign

0.74

PhyloP100

0.048

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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