1-115081783-A-G

Position:

• chr1-115081783-A-G

Variant summary

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

The NM_005725.6(TSPAN2):​c.69+7581T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 152,064 control chromosomes in the GnomAD database, including 29,017 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 0.61 (29017 hom., cov: 32)
• Consequence: TSPAN2 NM_005725.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.876

Genes affected

TSPAN2 (HGNC:20659): (tetraspanin 2) The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSPAN2	NM_005725.6	c.69+7581T>C		intron_variant		ENST00000369516.7	NP_005716.2
TSPAN2	NM_001308315.2	c.69+7581T>C		intron_variant			NP_001295244.1
TSPAN2	NM_001308316.2	c.69+7581T>C		intron_variant			NP_001295245.1
TSPAN2	XM_016999996.2	c.69+7581T>C		intron_variant			XP_016855485.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSPAN2	ENST00000369516.7	c.69+7581T>C		intron_variant		1	NM_005725.6	ENSP00000358529	P1
TSPAN2	ENST00000433172.3	c.51+7581T>C		intron_variant		1		ENSP00000415256
TSPAN2	ENST00000369515.6	c.69+7581T>C		intron_variant		3		ENSP00000358528

Frequencies

GnomAD3 genomes AF: 0.608 AC: 92411 AN: 151946 Hom.: 29014 Cov.: 32

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.595

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.655

Gnomad SAS AF: 0.554

Gnomad FIN AF: 0.622

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.614

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

GnomAD4 genome AF: 0.608 AC: 92442 AN: 152064 Hom.: 29017 Cov.: 32 AF XY: 0.603 AC XY: 44858 AN XY: 74350

Gnomad4 AFR AF: 0.450

Gnomad4 AMR AF: 0.595

Gnomad4 ASJ AF: 0.643

Gnomad4 EAS AF: 0.655

Gnomad4 SAS AF: 0.553

Gnomad4 FIN AF: 0.622

Gnomad4 NFE AF: 0.701

Gnomad4 OTH AF: 0.609

Alfa AF: 0.656 Hom.: 17218

Bravo AF: 0.601

Asia WGS AF: 0.587 AC: 2042 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	7.6
DANN	Benign	0.65

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: rs910623; hg19: chr1-115624404;