10-112628557-A-G

Variant names:

• chr10-112628557-A-G
• rs1033922
• NM_145206.4:c.428-39661A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145206.4(VTI1A):​c.428-39661A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 151,976 control chromosomes in the GnomAD database, including 26,756 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 0.58 (26756 hom., cov: 32)
• Consequence: VTI1A NM_145206.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.15
• Publications: 6 publications found

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]

LOC124902503 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145206.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VTI1A	NM_145206.4	MANE Select	c.428-39661A>G		intron	N/A	NP_660207.2	Q96AJ9-2
	VTI1A	NM_001318203.2		c.449-39661A>G		intron	N/A	NP_001305132.1	A0A994J5N6
	VTI1A	NM_001365711.1		c.449-39661A>G		intron	N/A	NP_001352640.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VTI1A	ENST00000393077.3	TSL:2 MANE Select	c.428-39661A>G		intron	N/A	ENSP00000376792.2	Q96AJ9-2
	VTI1A	ENST00000432306.5	TSL:1	c.428-39661A>G		intron	N/A	ENSP00000395017.1	Q96AJ9-1
	VTI1A	ENST00000705995.1		c.449-39661A>G		intron	N/A	ENSP00000516199.1	A0A994J5N6

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88253 AN: 151858 Hom.: 26719 Cov.: 32

Gnomad AFR AF: 0.755

Gnomad AMI AF: 0.590

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.553

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.581 AC: 88334 AN: 151976 Hom.: 26756 Cov.: 32 AF XY: 0.573 AC XY: 42599 AN XY: 74284

African (AFR) AF: 0.755 AC: 31306 AN: 41464

American (AMR) AF: 0.514 AC: 7853 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 1537 AN: 3466

East Asian (EAS) AF: 0.449 AC: 2318 AN: 5164

South Asian (SAS) AF: 0.396 AC: 1915 AN: 4830

European-Finnish (FIN) AF: 0.503 AC: 5302 AN: 10540

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.533 AC: 36236 AN: 67930

Other (OTH) AF: 0.554 AC: 1167 AN: 2106

Alfa AF: 0.538 Hom.: 45626

Bravo AF: 0.594

Asia WGS AF: 0.412 AC: 1431 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.033
DANN	Benign	0.45
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1033922;

hg19: chr10-114388316;