chr8-142231572-A-C

Variant names:

• chr8-142231572-A-C
• rs4129585
• NM_145003.5:c.1447-1993T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 75 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TSNARE1	NM_145003.5	c.1447-1993T>G		intron_variant	Intron 12 of 13	ENST00000524325.6	NP_659440.2
TSNARE1	NM_001363740.2	c.1450-1993T>G		intron_variant	Intron 12 of 13		NP_001350669.1
TSNARE1	NM_001366901.1	c.1444-1993T>G		intron_variant	Intron 12 of 13		NP_001353830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSNARE1	ENST00000524325.6	c.1447-1993T>G		intron_variant	Intron 12 of 13	2	NM_145003.5	ENSP00000428763.2
TSNARE1	ENST00000520166.5	c.1450-1993T>G		intron_variant	Intron 11 of 12	1		ENSP00000427770.2
TSNARE1	ENST00000662555.2	c.1915-1993T>G		intron_variant	Intron 12 of 13			ENSP00000499343.2
TSNARE1	ENST00000307180.4	c.1450-1993T>G		intron_variant	Intron 12 of 13	5		ENSP00000303437.4

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

African (AFR) AF: 0.876 AC: 36356 AN: 41494

American (AMR) AF: 0.701 AC: 10721 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.574 AC: 1993 AN: 3470

East Asian (EAS) AF: 0.743 AC: 3827 AN: 5148

South Asian (SAS) AF: 0.784 AC: 3781 AN: 4822

European-Finnish (FIN) AF: 0.578 AC: 6103 AN: 10562

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.556 AC: 37780 AN: 67930

Other (OTH) AF: 0.643 AC: 1360 AN: 2114

Alfa AF: 0.604 Hom.: 100937

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
PhyloP100		-0.056
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

Other links and lift over

dbSNP: rs4129585; hg19: chr8-143312933;