chr7-120815720-T-C

Variant names:

• chr7-120815720-T-C
• rs116938497
• NM_012338.4:c.360+9A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_012338.4(TSPAN12):​c.360+9A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0097 in 1,610,184 control chromosomes in the GnomAD database, including 109 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0076 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0099 (103 hom.)
• Consequence: TSPAN12 NM_012338.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.342
• Publications: 1 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 7-120815720-T-C is Benign according to our data. Variant chr7-120815720-T-C is described in ClinVar as Benign. ClinVar VariationId is 358763.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00761 (1160/152344) while in subpopulation NFE AF = 0.0114 (776/68034). AF 95% confidence interval is 0.0107. There are 6 homozygotes in GnomAd4. There are 526 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1160 AD,SD gene.

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.360+9A>G		intron	N/A	NP_036470.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPAN12	ENST00000222747.8	TSL:1 MANE Select	c.360+9A>G		intron	N/A	ENSP00000222747.3
	TSPAN12	ENST00000415871.5	TSL:5	c.360+9A>G		intron	N/A	ENSP00000397699.1
	TSPAN12	ENST00000854320.1		c.360+9A>G		intron	N/A	ENSP00000524379.1

Frequencies

GnomAD3 genomes AF: 0.00762 AC: 1160 AN: 152226 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00217

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0109

Gnomad ASJ AF: 0.0185

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.000753

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0114

Gnomad OTH AF: 0.0124

GnomAD2 exomes AF: 0.00777 AC: 1927 AN: 248058 AF XY: 0.00795

Gnomad AFR exome AF: 0.00182

Gnomad AMR exome AF: 0.00850

Gnomad ASJ exome AF: 0.0139

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000852

Gnomad NFE exome AF: 0.0119

Gnomad OTH exome AF: 0.00926

GnomAD4 exome AF: 0.00992 AC: 14458 AN: 1457840 Hom.: 103 Cov.: 30 AF XY: 0.00980 AC XY: 7109 AN XY: 725246

African (AFR) AF: 0.00162 AC: 54 AN: 33370

American (AMR) AF: 0.00864 AC: 384 AN: 44462

Ashkenazi Jewish (ASJ) AF: 0.0156 AC: 406 AN: 26044

East Asian (EAS) AF: 0.00 AC: 0 AN: 39606

South Asian (SAS) AF: 0.00200 AC: 172 AN: 85950

European-Finnish (FIN) AF: 0.00145 AC: 77 AN: 52938

Middle Eastern (MID) AF: 0.0151 AC: 87 AN: 5754

European-Non Finnish (NFE) AF: 0.0114 AC: 12675 AN: 1109470

Other (OTH) AF: 0.0100 AC: 603 AN: 60246

GnomAD4 genome AF: 0.00761 AC: 1160 AN: 152344 Hom.: 6 Cov.: 32 AF XY: 0.00706 AC XY: 526 AN XY: 74496

African (AFR) AF: 0.00216 AC: 90 AN: 41586

American (AMR) AF: 0.0109 AC: 167 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0185 AC: 64 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00186 AC: 9 AN: 4832

European-Finnish (FIN) AF: 0.000753 AC: 8 AN: 10626

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0114 AC: 776 AN: 68034

Other (OTH) AF: 0.0123 AC: 26 AN: 2112

Alfa AF: 0.0100 Hom.: 2

Bravo AF: 0.00848

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Exudative vitreoretinopathy 5 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	14
DANN	Benign	0.84
PhyloP100		0.34
Mutation Taster		=100/0	polymorphism

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: rs116938497; hg19: chr7-120455774;