rs12539888

Variant names:

• chr7-11495275-T-C
• rs12539888
• NM_015204.3:c.1823-13293A>G

Variant summary

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

The NM_015204.3(THSD7A):​c.1823-13293A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 152,018 control chromosomes in the GnomAD database, including 4,076 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 0.23 (4076 hom., cov: 33)
• Consequence: THSD7A NM_015204.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.173
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THSD7A	NM_015204.3	c.1823-13293A>G		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.1823-13293A>G		intron_variant	Intron 6 of 27	5	NM_015204.3	ENSP00000406482.2
ENSG00000230333	ENST00000445839.5	n.442-24777T>C		intron_variant	Intron 3 of 3	4
THSD7A	ENST00000497575.1	n.311+46144A>G		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34641 AN: 151900 Hom.: 4075 Cov.: 33

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.228 AC: 34660 AN: 152018 Hom.: 4076 Cov.: 33 AF XY: 0.225 AC XY: 16700 AN XY: 74290

African (AFR) AF: 0.215 AC: 8915 AN: 41488

American (AMR) AF: 0.180 AC: 2752 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 920 AN: 3470

East Asian (EAS) AF: 0.265 AC: 1371 AN: 5176

South Asian (SAS) AF: 0.278 AC: 1340 AN: 4818

European-Finnish (FIN) AF: 0.163 AC: 1728 AN: 10594

Middle Eastern (MID) AF: 0.322 AC: 94 AN: 292

European-Non Finnish (NFE) AF: 0.248 AC: 16812 AN: 67896

Other (OTH) AF: 0.243 AC: 512 AN: 2108

Alfa AF: 0.249 Hom.: 2887

Bravo AF: 0.226

Asia WGS AF: 0.281 AC: 972 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.58
DANN	Benign	0.60
PhyloP100		-0.17
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: rs12539888; hg19: chr7-11534902;