rs725588

Variant names:

• chr7-11659522-G-A
• rs725588
• NM_015204.3:c.191-22561C>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.191-22561C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 150,894 control chromosomes in the GnomAD database, including 22,940 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 0.55 (22940 hom., cov: 30)
• Consequence: THSD7A NM_015204.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0870
• Publications: 3 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THSD7A	NM_015204.3	c.191-22561C>T		intron_variant	Intron 1 of 27	ENST00000423059.9	NP_056019.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THSD7A	ENST00000423059.9	c.191-22561C>T		intron_variant	Intron 1 of 27	5	NM_015204.3	ENSP00000406482.2
THSD7A	ENST00000480061.1	n.218-22561C>T		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.548 AC: 82569 AN: 150776 Hom.: 22900 Cov.: 30

Gnomad AFR AF: 0.581

Gnomad AMI AF: 0.584

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.458

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.544

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

GnomAD4 genome AF: 0.548 AC: 82663 AN: 150894 Hom.: 22940 Cov.: 30 AF XY: 0.538 AC XY: 39628 AN XY: 73706

African (AFR) AF: 0.582 AC: 24015 AN: 41280

American (AMR) AF: 0.608 AC: 9160 AN: 15066

Ashkenazi Jewish (ASJ) AF: 0.458 AC: 1577 AN: 3440

East Asian (EAS) AF: 0.495 AC: 2530 AN: 5110

South Asian (SAS) AF: 0.342 AC: 1642 AN: 4802

European-Finnish (FIN) AF: 0.402 AC: 4209 AN: 10482

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.560 AC: 37733 AN: 67424

Other (OTH) AF: 0.539 AC: 1125 AN: 2086

Alfa AF: 0.550 Hom.: 7636

Bravo AF: 0.571

Asia WGS AF: 0.409 AC: 1422 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.8
DANN	Benign	0.27
PhyloP100		0.087
Mutation Taster		=99/1	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: rs725588; hg19: chr7-11699149;