rs12539888

Positions:

• chr7-11495275-T-C

Variant summary

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

The NM_015204.3(THSD7A):​c.1823-13293A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 152,018 control chromosomes in the GnomAD database, including 4,076 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 0.23 (4076 hom., cov: 33)
• Consequence: THSD7A NM_015204.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.173

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THSD7A	NM_015204.3	c.1823-13293A>G		intron_variant		ENST00000423059.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THSD7A	ENST00000423059.9	c.1823-13293A>G		intron_variant		5	NM_015204.3	P1
	ENST00000445839.5	n.442-24777T>C		intron_variant, non_coding_transcript_variant		4
THSD7A	ENST00000497575.1	n.311+46144A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34641 AN: 151900 Hom.: 4075 Cov.: 33

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.228 AC: 34660 AN: 152018 Hom.: 4076 Cov.: 33 AF XY: 0.225 AC XY: 16700 AN XY: 74290

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.265

Gnomad4 EAS AF: 0.265

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.243

Alfa AF: 0.248 Hom.: 2613

Bravo AF: 0.226

Asia WGS AF: 0.281 AC: 972 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.58
DANN	Benign	0.60

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: rs12539888; hg19: chr7-11534902;