chr8-142231572-A-C

Position:

• chr8-142231572-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145003.5(TSNARE1):​c.1447-1993T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 152,034 control chromosomes in the GnomAD database, including 36,139 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 0.68 (36139 hom., cov: 32)
• Consequence: TSNARE1 NM_145003.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0560

Genes affected

TSNARE1 (HGNC:26437): (t-SNARE domain containing 1) Predicted to enable SNAP receptor activity and SNARE binding activity. Predicted to be involved in intracellular protein transport; vesicle docking; and vesicle fusion. Predicted to be located in membrane. Predicted to be part of SNARE complex. Predicted to be active in endomembrane system. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSNARE1	NM_145003.5	c.1447-1993T>G		intron_variant		ENST00000524325.6	NP_659440.2
TSNARE1	NM_001363740.2	c.1450-1993T>G		intron_variant			NP_001350669.1
TSNARE1	NM_001366901.1	c.1444-1993T>G		intron_variant			NP_001353830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSNARE1	ENST00000524325.6	c.1447-1993T>G		intron_variant		2	NM_145003.5	ENSP00000428763	A2
TSNARE1	ENST00000520166.5	c.1450-1993T>G		intron_variant		1		ENSP00000427770	P2
TSNARE1	ENST00000307180.4	c.1450-1993T>G		intron_variant		5		ENSP00000303437	P2

Frequencies

GnomAD3 genomes AF: 0.675 AC: 102510 AN: 151914 Hom.: 36085 Cov.: 32

Gnomad AFR AF: 0.876

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.701

Gnomad ASJ AF: 0.574

Gnomad EAS AF: 0.744

Gnomad SAS AF: 0.785

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.642

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

GnomAD4 genome AF: 0.675 AC: 102626 AN: 152034 Hom.: 36139 Cov.: 32 AF XY: 0.678 AC XY: 50378 AN XY: 74288

Gnomad4 AFR AF: 0.876

Gnomad4 AMR AF: 0.701

Gnomad4 ASJ AF: 0.574

Gnomad4 EAS AF: 0.743

Gnomad4 SAS AF: 0.784

Gnomad4 FIN AF: 0.578

Gnomad4 NFE AF: 0.556

Gnomad4 OTH AF: 0.643

Alfa AF: 0.584 Hom.: 35864

Bravo AF: 0.688

Asia WGS AF: 0.742 AC: 2585 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	6.2
DANN	Benign	0.44

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

LitVar

Other links and lift over

dbSNP: rs4129585; hg19: chr8-143312933;