rs53

Positions:

• chr7-11537998-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015204.3(THSD7A):​c.1822+3421G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,134 control chromosomes in the GnomAD database, including 3,608 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 0.19 (3608 hom., cov: 32)
• Consequence: THSD7A NM_015204.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.59

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THSD7A	NM_015204.3	c.1822+3421G>A		intron_variant		ENST00000423059.9	NP_056019.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THSD7A	ENST00000423059.9	c.1822+3421G>A		intron_variant		5	NM_015204.3	ENSP00000406482	P1
THSD7A	ENST00000497575.1	n.311+3421G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29093 AN: 152016 Hom.: 3603 Cov.: 32

Gnomad AFR AF: 0.0517

Gnomad AMI AF: 0.0791

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.191 AC: 29097 AN: 152134 Hom.: 3608 Cov.: 32 AF XY: 0.193 AC XY: 14386 AN XY: 74376

Gnomad4 AFR AF: 0.0515

Gnomad4 AMR AF: 0.390

Gnomad4 ASJ AF: 0.242

Gnomad4 EAS AF: 0.188

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.227

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.219

Alfa AF: 0.229 Hom.: 8512

Bravo AF: 0.199

Asia WGS AF: 0.164 AC: 572 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.10
DANN	Benign	0.49

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: rs53; hg19: chr7-11577625;