rs10486146

Positions:

• chr7-11620699-C-A
• chr7-11620699-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.1022+15431G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,154 control chromosomes in the GnomAD database, including 2,669 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 0.11 (2669 hom., cov: 32)
• Consequence: THSD7A NM_015204.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.397

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THSD7A	NM_015204.3	c.1022+15431G>T		intron_variant		ENST00000423059.9	NP_056019.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THSD7A	ENST00000423059.9	c.1022+15431G>T		intron_variant		5	NM_015204.3	ENSP00000406482	P1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16713 AN: 152036 Hom.: 2660 Cov.: 32

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0458

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.0723

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.00246

Gnomad OTH AF: 0.0822

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

GnomAD4 genome AF: 0.110 AC: 16764 AN: 152154 Hom.: 2669 Cov.: 32 AF XY: 0.110 AC XY: 8155 AN XY: 74398

Gnomad4 AFR AF: 0.338

Gnomad4 AMR AF: 0.0457

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.252

Gnomad4 SAS AF: 0.0728

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00246

Gnomad4 OTH AF: 0.0818

Alfa AF: 0.0169 Hom.: 525

Bravo AF: 0.123

Asia WGS AF: 0.137 AC: 476 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.65

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: rs10486146; hg19: chr7-11660326;