rs12673692

chr7-11528903-G-Achr7-11528903-G-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+12516C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 151,738 control chromosomes in the GnomAD database, including 7,212 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 0.30 (7212 hom., cov: 32)
• Consequence: THSD7A NM_015204.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26

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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THSD7A	NM_015204.3	c.1822+12516C>T		intron_variant		ENST00000423059.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THSD7A	ENST00000423059.9	c.1822+12516C>T		intron_variant		5	NM_015204.3	P1
THSD7A	ENST00000497575.1	n.311+12516C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46220 AN: 151620 Hom.: 7199 Cov.: 32

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.291

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

GnomAD4 genome AF: 0.305 AC: 46269 AN: 151738 Hom.: 7212 Cov.: 32 AF XY: 0.306 AC XY: 22649 AN XY: 74124

Gnomad4 AFR AF: 0.368

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.312

Gnomad4 EAS AF: 0.353

Gnomad4 SAS AF: 0.404

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.283

Gnomad4 OTH AF: 0.294

Alfa AF: 0.282 Hom.: 5961

Bravo AF: 0.303

Asia WGS AF: 0.365 AC: 1266 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.073
Dann	Benign	0.71

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: rs12673692; hg19: chr7-11568530;