chr7-120829636-T-A

Variant names:

• chr7-120829636-T-A
• rs6466759
• NM_012338.4:c.285+9141A>T

Variant summary

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

The NM_012338.4(TSPAN12):​c.285+9141A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 151,970 control chromosomes in the GnomAD database, including 14,009 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 0.39 (14009 hom., cov: 32)
• Consequence: TSPAN12 NM_012338.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57
• Publications: 4 publications found

Genes affected

TSPAN12 (HGNC:21641): (tetraspanin 12) 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. [provided by RefSeq, Jul 2008]

TSPAN12 Gene-Disease associations (from GenCC):

• exudative vitreoretinopathy 5

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• TSPAN12-related vitreoretinopathy

  Inheritance: SD Classification: DEFINITIVE Submitted by: ClinGen
• exudative vitreoretinopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012338.4. 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
	TSPAN12	NM_012338.4	MANE Select	c.285+9141A>T		intron	N/A	NP_036470.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPAN12	ENST00000222747.8	TSL:1 MANE Select	c.285+9141A>T		intron	N/A	ENSP00000222747.3
	TSPAN12	ENST00000415871.5	TSL:5	c.285+9141A>T		intron	N/A	ENSP00000397699.1
	TSPAN12	ENST00000441017.5	TSL:4	c.285+9141A>T		intron	N/A	ENSP00000411158.1

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59296 AN: 151852 Hom.: 13965 Cov.: 32

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.342

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

GnomAD4 genome AF: 0.391 AC: 59412 AN: 151970 Hom.: 14009 Cov.: 32 AF XY: 0.394 AC XY: 29244 AN XY: 74276

African (AFR) AF: 0.665 AC: 27576 AN: 41446

American (AMR) AF: 0.347 AC: 5292 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 794 AN: 3470

East Asian (EAS) AF: 0.376 AC: 1936 AN: 5154

South Asian (SAS) AF: 0.222 AC: 1070 AN: 4828

European-Finnish (FIN) AF: 0.412 AC: 4344 AN: 10548

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.256 AC: 17363 AN: 67950

Other (OTH) AF: 0.349 AC: 738 AN: 2112

Alfa AF: 0.201 Hom.: 457

Bravo AF: 0.404

Asia WGS AF: 0.358 AC: 1245 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.14
DANN	Benign	0.67
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs6466759; hg19: chr7-120469690;