7-11376653-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_015204.3(THSD7A):c.4806G>A(p.Gly1602=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0009 in 1,572,472 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00072 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00092 (3 hom.)
• Consequence: THSD7A NM_015204.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0290

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 Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 7-11376653-C-T is Benign according to our data. Variant chr7-11376653-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 715898.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.029 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THSD7A	NM_015204.3	c.4806G>A	p.Gly1602=	synonymous_variant	27/28	ENST00000423059.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THSD7A	ENST00000423059.9	c.4806G>A	p.Gly1602=	synonymous_variant	27/28	5	NM_015204.3	P1
	ENST00000445839.5	n.247-2634C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.000723 AC: 110 AN: 152066 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00322

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000780

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.000795 AC: 149 AN: 187324 Hom.: 2 AF XY: 0.000804 AC XY: 80 AN XY: 99510

Gnomad AFR exome AF: 0.0000940

Gnomad AMR exome AF: 0.00138

Gnomad ASJ exome AF: 0.000677

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000249

Gnomad FIN exome AF: 0.0000541

Gnomad NFE exome AF: 0.00113

Gnomad OTH exome AF: 0.00143

GnomAD4 exome AF: 0.000920 AC: 1307 AN: 1420288 Hom.: 3 Cov.: 29 AF XY: 0.000942 AC XY: 662 AN XY: 702474

Gnomad4 AFR exome AF: 0.000186

Gnomad4 AMR exome AF: 0.00144

Gnomad4 ASJ exome AF: 0.000395

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000212

Gnomad4 FIN exome AF: 0.000118

Gnomad4 NFE exome AF: 0.00104

Gnomad4 OTH exome AF: 0.00107

GnomAD4 genome AF: 0.000716 AC: 109 AN: 152184 Hom.: 0 Cov.: 32 AF XY: 0.000833 AC XY: 62 AN XY: 74394

Gnomad4 AFR AF: 0.0000963

Gnomad4 AMR AF: 0.00321

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000765

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000631 Hom.: 0

Bravo AF: 0.00109

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2022	THSD7A: BP4, BP7 -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Apr 13, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
Cadd	Benign	6.1
Dann	Benign	0.77

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

Publications

LitVar

Other links and lift over

dbSNP: rs144799458; hg19: chr7-11416280;