7-120824495-C-T

Variant names:

• chr7-120824495-C-T
• rs6953454
• NM_012338.4:c.286-8692G>A

Variant summary

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

The NM_012338.4(TSPAN12):​c.286-8692G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 151,778 control chromosomes in the GnomAD database, including 14,183 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 0.40 (14183 hom., cov: 31)
• Consequence: TSPAN12 NM_012338.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.185
• 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: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• TSPAN12-related exudative 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=-0.97).
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPAN12	NM_012338.4	MANE Select	c.286-8692G>A		intron	N/A	NP_036470.1	O95859-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPAN12	ENST00000222747.8	TSL:1 MANE Select	c.286-8692G>A		intron	N/A	ENSP00000222747.3	O95859-1
	TSPAN12	ENST00000415871.5	TSL:5	c.286-8692G>A		intron	N/A	ENSP00000397699.1	O95859-1
	TSPAN12	ENST00000854320.1		c.286-8692G>A		intron	N/A	ENSP00000524379.1

Frequencies

GnomAD3 genomes AF: 0.395 AC: 59868 AN: 151660 Hom.: 14139 Cov.: 31

Gnomad AFR AF: 0.666

Gnomad AMI AF: 0.256

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.344

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

GnomAD4 genome AF: 0.395 AC: 59986 AN: 151778 Hom.: 14183 Cov.: 31 AF XY: 0.398 AC XY: 29493 AN XY: 74176

African (AFR) AF: 0.666 AC: 27569 AN: 41390

American (AMR) AF: 0.349 AC: 5319 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 795 AN: 3464

East Asian (EAS) AF: 0.376 AC: 1936 AN: 5148

South Asian (SAS) AF: 0.222 AC: 1072 AN: 4820

European-Finnish (FIN) AF: 0.414 AC: 4333 AN: 10472

Middle Eastern (MID) AF: 0.241 AC: 70 AN: 290

European-Non Finnish (NFE) AF: 0.264 AC: 17915 AN: 67914

Other (OTH) AF: 0.352 AC: 744 AN: 2116

Alfa AF: 0.205 Hom.: 466

Bravo AF: 0.408

Asia WGS AF: 0.360 AC: 1253 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.95
DANN	Benign	0.38
PhyloP100		-0.18
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: rs6953454; hg19: chr7-120464549;