7-120795584-T-C

Variant names:

• chr7-120795584-T-C
• rs41624
• NM_012338.4:c.613-6687A>G

Variant summary

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

The NM_012338.4(TSPAN12):​c.613-6687A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.665 in 152,108 control chromosomes in the GnomAD database, including 33,988 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 0.67 (33988 hom., cov: 33)
• Consequence: TSPAN12 NM_012338.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0650
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPAN12	NM_012338.4	c.613-6687A>G		intron_variant	Intron 7 of 7	ENST00000222747.8	NP_036470.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSPAN12	ENST00000222747.8	c.613-6687A>G		intron_variant	Intron 7 of 7	1	NM_012338.4	ENSP00000222747.3
TSPAN12	ENST00000415871.5	c.613-6687A>G		intron_variant	Intron 8 of 8	5		ENSP00000397699.1
TSPAN12	ENST00000450414.5	n.*463-6687A>G		intron_variant	Intron 5 of 5	5		ENSP00000397411.1

Frequencies

GnomAD3 genomes AF: 0.666 AC: 101152 AN: 151990 Hom.: 33978 Cov.: 33

Gnomad AFR AF: 0.585

Gnomad AMI AF: 0.745

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.767

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.769

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.713

Gnomad OTH AF: 0.695

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

GnomAD4 genome AF: 0.665 AC: 101205 AN: 152108 Hom.: 33988 Cov.: 33 AF XY: 0.661 AC XY: 49174 AN XY: 74348

African (AFR) AF: 0.585 AC: 24271 AN: 41476

American (AMR) AF: 0.673 AC: 10287 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.767 AC: 2664 AN: 3472

East Asian (EAS) AF: 0.618 AC: 3202 AN: 5178

South Asian (SAS) AF: 0.771 AC: 3722 AN: 4828

European-Finnish (FIN) AF: 0.587 AC: 6208 AN: 10568

Middle Eastern (MID) AF: 0.803 AC: 236 AN: 294

European-Non Finnish (NFE) AF: 0.713 AC: 48483 AN: 67984

Other (OTH) AF: 0.689 AC: 1453 AN: 2110

Alfa AF: 0.676 Hom.: 9362

Bravo AF: 0.665

Asia WGS AF: 0.655 AC: 2277 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	0.31
DANN	Benign	0.36
PhyloP100		-0.065
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: rs41624; hg19: chr7-120435638;