1-115081783-A-G

Variant names:

• chr1-115081783-A-G
• rs910623
• NM_005725.6:c.69+7581T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005725.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPAN2	NM_005725.6	MANE Select	c.69+7581T>C		intron	N/A	NP_005716.2
	TSPAN2	NM_001308315.2		c.69+7581T>C		intron	N/A	NP_001295244.1
	TSPAN2	NM_001308316.2		c.69+7581T>C		intron	N/A	NP_001295245.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPAN2	ENST00000369516.7	TSL:1 MANE Select	c.69+7581T>C		intron	N/A	ENSP00000358529.2
	TSPAN2	ENST00000433172.3	TSL:1	c.51+7581T>C		intron	N/A	ENSP00000415256.1
	TSPAN2	ENST00000369515.6	TSL:3	c.69+7581T>C		intron	N/A	ENSP00000358528.2

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

African (AFR) AF: 0.450 AC: 18672 AN: 41468

American (AMR) AF: 0.595 AC: 9098 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.643 AC: 2231 AN: 3470

East Asian (EAS) AF: 0.655 AC: 3385 AN: 5170

South Asian (SAS) AF: 0.553 AC: 2665 AN: 4822

European-Finnish (FIN) AF: 0.622 AC: 6555 AN: 10546

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.701 AC: 47693 AN: 67988

Other (OTH) AF: 0.609 AC: 1289 AN: 2116

Alfa AF: 0.658 Hom.: 19134

Bravo AF: 0.601

Asia WGS AF: 0.587 AC: 2042 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	7.6
DANN	Benign	0.65
PhyloP100		0.88
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: rs910623; hg19: chr1-115624404;