rs2074597

Positions:

• chr7-11637067-C-A
• chr7-11637067-C-G

Variant summary

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

The NM_015204.3(THSD7A):​c.191-106G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 1,045,734 control chromosomes in the GnomAD database, including 29,847 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 0.29 (7542 hom., cov: 32)
  • Exomes 𝑓: 0.21 (22305 hom.)
• Consequence: THSD7A NM_015204.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.475

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THSD7A	NM_015204.3	c.191-106G>T		intron_variant		ENST00000423059.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THSD7A	ENST00000423059.9	c.191-106G>T		intron_variant		5	NM_015204.3	P1
THSD7A	ENST00000480061.1	n.218-106G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43880 AN: 151914 Hom.: 7527 Cov.: 32

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.258

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.282

GnomAD4 exome AF: 0.208 AC: 185548 AN: 893702 Hom.: 22305 AF XY: 0.207 AC XY: 93230 AN XY: 450496

Gnomad4 AFR exome AF: 0.481

Gnomad4 AMR exome AF: 0.251

Gnomad4 ASJ exome AF: 0.251

Gnomad4 EAS exome AF: 0.484

Gnomad4 SAS exome AF: 0.212

Gnomad4 FIN exome AF: 0.209

Gnomad4 NFE exome AF: 0.179

Gnomad4 OTH exome AF: 0.233

GnomAD4 genome AF: 0.289 AC: 43942 AN: 152032 Hom.: 7542 Cov.: 32 AF XY: 0.289 AC XY: 21501 AN XY: 74324

Gnomad4 AFR AF: 0.472

Gnomad4 AMR AF: 0.263

Gnomad4 ASJ AF: 0.258

Gnomad4 EAS AF: 0.460

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.216

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.279

Alfa AF: 0.200 Hom.: 4406

Bravo AF: 0.304

Asia WGS AF: 0.330 AC: 1148 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	14
DANN	Benign	0.67

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: rs2074597; hg19: chr7-11676694; COSMIC: COSV70267893;