7-11541507-T-C

Position:

• chr7-11541507-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_015204.3(THSD7A):​c.1734A>G​(p.Ala578=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 1,613,206 control chromosomes in the GnomAD database, including 150,358 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 0.44 (14508 hom., cov: 32)
  • Exomes 𝑓: 0.43 (135850 hom.)
• Consequence: THSD7A NM_015204.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.467

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP7: Synonymous conserved (PhyloP=0.467 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THSD7A	NM_015204.3	c.1734A>G	p.Ala578=	synonymous_variant	6/28	ENST00000423059.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THSD7A	ENST00000423059.9	c.1734A>G	p.Ala578=	synonymous_variant	6/28	5	NM_015204.3	P1
THSD7A	ENST00000497575.1	n.223A>G		non_coding_transcript_exon_variant	2/4	5

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66047 AN: 151798 Hom.: 14497 Cov.: 32

Gnomad AFR AF: 0.474

Gnomad AMI AF: 0.394

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.431

GnomAD3 exomes AF: 0.425 AC: 105756 AN: 248892 Hom.: 22843 AF XY: 0.430 AC XY: 58102 AN XY: 134994

Gnomad AFR exome AF: 0.482

Gnomad AMR exome AF: 0.369

Gnomad ASJ exome AF: 0.467

Gnomad EAS exome AF: 0.505

Gnomad SAS exome AF: 0.481

Gnomad FIN exome AF: 0.332

Gnomad NFE exome AF: 0.419

Gnomad OTH exome AF: 0.438

GnomAD4 exome AF: 0.429 AC: 626991 AN: 1461290 Hom.: 135850 Cov.: 51 AF XY: 0.431 AC XY: 313608 AN XY: 726944

Gnomad4 AFR exome AF: 0.484

Gnomad4 AMR exome AF: 0.373

Gnomad4 ASJ exome AF: 0.476

Gnomad4 EAS exome AF: 0.492

Gnomad4 SAS exome AF: 0.484

Gnomad4 FIN exome AF: 0.338

Gnomad4 NFE exome AF: 0.425

Gnomad4 OTH exome AF: 0.446

GnomAD4 genome AF: 0.435 AC: 66092 AN: 151916 Hom.: 14508 Cov.: 32 AF XY: 0.433 AC XY: 32158 AN XY: 74264

Gnomad4 AFR AF: 0.474

Gnomad4 AMR AF: 0.386

Gnomad4 ASJ AF: 0.466

Gnomad4 EAS AF: 0.517

Gnomad4 SAS AF: 0.489

Gnomad4 FIN AF: 0.331

Gnomad4 NFE AF: 0.427

Gnomad4 OTH AF: 0.431

Alfa AF: 0.431 Hom.: 18223

Bravo AF: 0.438

Asia WGS AF: 0.458 AC: 1595 AN: 3478

EpiCase AF: 0.430

EpiControl AF: 0.429

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	2.4
DANN	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2074603; hg19: chr7-11581134; COSMIC: COSV70262199;