rs40

Variant names:

• chr7-11548657-C-T
• rs40
• NM_015204.3:c.1454-5540G>A

Variant summary

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

The NM_015204.3(THSD7A):​c.1454-5540G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 151,838 control chromosomes in the GnomAD database, including 12,146 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 0.39 (12146 hom., cov: 32)
• Consequence: THSD7A NM_015204.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.290
• Publications: 0 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THSD7A	NM_015204.3	c.1454-5540G>A		intron_variant	Intron 4 of 27	ENST00000423059.9	NP_056019.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THSD7A	ENST00000423059.9	c.1454-5540G>A		intron_variant	Intron 4 of 27	5	NM_015204.3	ENSP00000406482.2

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58746 AN: 151720 Hom.: 12141 Cov.: 32

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.423

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

GnomAD4 genome AF: 0.387 AC: 58773 AN: 151838 Hom.: 12146 Cov.: 32 AF XY: 0.388 AC XY: 28801 AN XY: 74248

African (AFR) AF: 0.272 AC: 11242 AN: 41392

American (AMR) AF: 0.594 AC: 9073 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.517 AC: 1791 AN: 3466

East Asian (EAS) AF: 0.361 AC: 1859 AN: 5154

South Asian (SAS) AF: 0.288 AC: 1387 AN: 4822

European-Finnish (FIN) AF: 0.382 AC: 4026 AN: 10534

Middle Eastern (MID) AF: 0.386 AC: 112 AN: 290

European-Non Finnish (NFE) AF: 0.414 AC: 28120 AN: 67898

Other (OTH) AF: 0.424 AC: 892 AN: 2106

Alfa AF: 0.412 Hom.: 41374

Bravo AF: 0.400

Asia WGS AF: 0.340 AC: 1190 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.1
DANN	Benign	0.60
PhyloP100		0.29
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: rs40; hg19: chr7-11588284;