rs22

chr7-11556875-A-Gchr7-11556875-A-T

Variant summary

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

The NM_015204.3(THSD7A):c.1454-13758T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 151,692 control chromosomes in the GnomAD database, including 28,332 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 0.61 (28332 hom., cov: 31)
• Consequence: THSD7A NM_015204.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55

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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THSD7A	NM_015204.3	c.1454-13758T>C		intron_variant		ENST00000423059.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THSD7A	ENST00000423059.9	c.1454-13758T>C		intron_variant		5	NM_015204.3	P1

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91712 AN: 151574 Hom.: 28296 Cov.: 31

Gnomad AFR AF: 0.723

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.658

Gnomad ASJ AF: 0.605

Gnomad EAS AF: 0.560

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.676

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.613

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

GnomAD4 genome AF: 0.605 AC: 91799 AN: 151692 Hom.: 28332 Cov.: 31 AF XY: 0.602 AC XY: 44650 AN XY: 74136

Gnomad4 AFR AF: 0.724

Gnomad4 AMR AF: 0.658

Gnomad4 ASJ AF: 0.605

Gnomad4 EAS AF: 0.560

Gnomad4 SAS AF: 0.533

Gnomad4 FIN AF: 0.510

Gnomad4 NFE AF: 0.547

Gnomad4 OTH AF: 0.612

Alfa AF: 0.584 Hom.: 3249

Bravo AF: 0.622

Asia WGS AF: 0.534 AC: 1852 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.2
Dann	Benign	0.29

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: rs22; hg19: chr7-11596502; COSMIC: COSV70274355;