7-11375882-TA-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_015204.3(THSD7A):c.4890-5del variant causes a splice region, splice polypyrimidine tract, intron change. The variant allele was found at a frequency of 0.00394 in 1,612,216 control chromosomes in the GnomAD database, including 19 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0026 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0041 (17 hom.)
• Consequence: THSD7A NM_015204.3 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.79

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]

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 7-11375882-TA-T is Benign according to our data. Variant chr7-11375882-TA-T is described in ClinVar as [Benign]. Clinvar id is 773490.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THSD7A	NM_015204.3	c.4890-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000423059.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THSD7A	ENST00000423059.9	c.4890-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_015204.3	P1
	ENST00000445839.5	n.247-3398del		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.00256 AC: 389 AN: 151934 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000773

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00125

Gnomad ASJ AF: 0.0196

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00365

Gnomad OTH AF: 0.00528

GnomAD3 exomes AF: 0.00295 AC: 733 AN: 248458 Hom.: 3 AF XY: 0.00327 AC XY: 441 AN XY: 134808

Gnomad AFR exome AF: 0.000648

Gnomad AMR exome AF: 0.00166

Gnomad ASJ exome AF: 0.0184

Gnomad EAS exome AF: 0.0000558

Gnomad SAS exome AF: 0.00157

Gnomad FIN exome AF: 0.000279

Gnomad NFE exome AF: 0.00361

Gnomad OTH exome AF: 0.00332

GnomAD4 exome AF: 0.00408 AC: 5957 AN: 1460164 Hom.: 17 Cov.: 30 AF XY: 0.00410 AC XY: 2979 AN XY: 726340

Gnomad4 AFR exome AF: 0.000629

Gnomad4 AMR exome AF: 0.00197

Gnomad4 ASJ exome AF: 0.0184

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00202

Gnomad4 FIN exome AF: 0.000468

Gnomad4 NFE exome AF: 0.00441

Gnomad4 OTH exome AF: 0.00415

GnomAD4 genome AF: 0.00255 AC: 388 AN: 152052 Hom.: 2 Cov.: 32 AF XY: 0.00231 AC XY: 172 AN XY: 74324

Gnomad4 AFR AF: 0.000771

Gnomad4 AMR AF: 0.00125

Gnomad4 ASJ AF: 0.0196

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000831

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00365

Gnomad4 OTH AF: 0.00522

Alfa AF: 0.00317 Hom.: 1

Bravo AF: 0.00278

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.00465

EpiControl AF: 0.00487

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs568171674; hg19: chr7-11415509;