chrX-38616132-A-G

Variant names:

• chrX-38616132-A-G
• rs5917609
• NM_004615.4:c.82-49989A>G

Variant summary

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

The NM_004615.4(TSPAN7):​c.82-49989A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0461 in 112,378 control chromosomes in the GnomAD database, including 93 homozygotes. There are 1,455 hemizygotes in GnomAD. 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 0.046 (93 hom., 1455 hem., cov: 22)
• Consequence: TSPAN7 NM_004615.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.380
• Publications: 1 publications found

Genes affected

TSPAN7 (HGNC:11854): (tetraspanin 7) 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. This encoded protein is a cell surface glycoprotein and may have a role in the control of neurite outgrowth. It is known to complex with integrins. This gene is associated with X-linked cognitive disability and neuropsychiatric diseases such as Huntington's chorea, fragile X syndrome and myotonic dystrophy. [provided by RefSeq, Jul 2008]

TSPAN7 Gene-Disease associations (from GenCC):

• intellectual disability, X-linked 58

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• non-syndromic X-linked intellectual disability

  Inheritance: XL Classification: MODERATE, SUPPORTIVE Submitted by: ClinGen, Orphanet

ENSG00000250349 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPAN7	NM_004615.4	c.82-49989A>G		intron_variant	Intron 1 of 7	ENST00000378482.7	NP_004606.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSPAN7	ENST00000378482.7	c.82-49989A>G		intron_variant	Intron 1 of 7	1	NM_004615.4	ENSP00000367743.2
ENSG00000250349	ENST00000465127.1	c.172-49989A>G		intron_variant	Intron 3 of 8	5		ENSP00000417050.1

Frequencies

GnomAD3 genomes AF: 0.0460 AC: 5167 AN: 112326 Hom.: 93 Cov.: 22

Gnomad AFR AF: 0.0586

Gnomad AMI AF: 0.0145

Gnomad AMR AF: 0.0312

Gnomad ASJ AF: 0.0177

Gnomad EAS AF: 0.000831

Gnomad SAS AF: 0.0136

Gnomad FIN AF: 0.0441

Gnomad MID AF: 0.0125

Gnomad NFE AF: 0.0487

Gnomad OTH AF: 0.0401

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

GnomAD4 genome AF: 0.0461 AC: 5180 AN: 112378 Hom.: 93 Cov.: 22 AF XY: 0.0421 AC XY: 1455 AN XY: 34550

African (AFR) AF: 0.0589 AC: 1821 AN: 30902

American (AMR) AF: 0.0312 AC: 333 AN: 10670

Ashkenazi Jewish (ASJ) AF: 0.0177 AC: 47 AN: 2650

East Asian (EAS) AF: 0.000833 AC: 3 AN: 3600

South Asian (SAS) AF: 0.0133 AC: 36 AN: 2703

European-Finnish (FIN) AF: 0.0441 AC: 272 AN: 6165

Middle Eastern (MID) AF: 0.0137 AC: 3 AN: 219

European-Non Finnish (NFE) AF: 0.0487 AC: 2594 AN: 53239

Other (OTH) AF: 0.0396 AC: 61 AN: 1542

Alfa AF: 0.0462 Hom.: 2420

Bravo AF: 0.0436

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.50
DANN	Benign	0.41
PhyloP100		-0.38
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: rs5917609; hg19: chrX-38475385;