rs10486135

Variant names:

• chr7-11488873-C-A
• rs10486135
• NM_015204.3:c.1823-6891G>T

Variant summary

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

The NM_015204.3(THSD7A):​c.1823-6891G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 151,858 control chromosomes in the GnomAD database, including 12,478 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 (12478 hom., cov: 32)
• Consequence: THSD7A NM_015204.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 8 publications found

Genes affected

THSD7A (HGNC:22207): (thrombospondin type 1 domain containing 7A) The protein encoded by this gene is found almost exclusively in endothelial cells from placenta and umbilical cord. The encoded protein appears to interact with alpha(V)beta(3) integrin and paxillin to inhibit endothelial cell migration and tube formation. This protein may be involved in cytoskeletal organization. Variations in this gene may be associated with low bone mineral density in osteoporosis. [provided by RefSeq, Aug 2010]

ENSG00000230333 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THSD7A	NM_015204.3	c.1823-6891G>T		intron_variant	Intron 6 of 27	ENST00000423059.9	NP_056019.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THSD7A	ENST00000423059.9	c.1823-6891G>T		intron_variant	Intron 6 of 27	5	NM_015204.3	ENSP00000406482.2
ENSG00000230333	ENST00000445839.5	n.442-31179C>A		intron_variant	Intron 3 of 3	4
THSD7A	ENST00000497575.1	n.312-41449G>T		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61033 AN: 151740 Hom.: 12459 Cov.: 32

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.410

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

GnomAD4 genome AF: 0.402 AC: 61108 AN: 151858 Hom.: 12478 Cov.: 32 AF XY: 0.398 AC XY: 29515 AN XY: 74228

African (AFR) AF: 0.435 AC: 18032 AN: 41416

American (AMR) AF: 0.349 AC: 5320 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1383 AN: 3466

East Asian (EAS) AF: 0.305 AC: 1572 AN: 5158

South Asian (SAS) AF: 0.469 AC: 2262 AN: 4820

European-Finnish (FIN) AF: 0.293 AC: 3088 AN: 10550

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.412 AC: 27994 AN: 67900

Other (OTH) AF: 0.411 AC: 869 AN: 2114

Alfa AF: 0.412 Hom.: 43676

Bravo AF: 0.405

Asia WGS AF: 0.411 AC: 1425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.75
PhyloP100		-1.1
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: rs10486135; hg19: chr7-11528500;