7-11573958-A-G

Position:

• chr7-11573958-A-G

Variant summary

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

The NM_015204.3(THSD7A):​c.1453+16502T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 152,036 control chromosomes in the GnomAD database, including 7,784 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 0.32 (7784 hom., cov: 32)
• Consequence: THSD7A NM_015204.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.292

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THSD7A	NM_015204.3	c.1453+16502T>C		intron_variant		ENST00000423059.9	NP_056019.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THSD7A	ENST00000423059.9	c.1453+16502T>C		intron_variant		5	NM_015204.3	ENSP00000406482	P1

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48335 AN: 151918 Hom.: 7773 Cov.: 32

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.318 AC: 48364 AN: 152036 Hom.: 7784 Cov.: 32 AF XY: 0.319 AC XY: 23717 AN XY: 74330

Gnomad4 AFR AF: 0.313

Gnomad4 AMR AF: 0.313

Gnomad4 ASJ AF: 0.315

Gnomad4 EAS AF: 0.358

Gnomad4 SAS AF: 0.422

Gnomad4 FIN AF: 0.275

Gnomad4 NFE AF: 0.320

Gnomad4 OTH AF: 0.312

Alfa AF: 0.327 Hom.: 2967

Bravo AF: 0.319

Asia WGS AF: 0.367 AC: 1270 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.2
DANN	Benign	0.39

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: rs7778918; hg19: chr7-11613585;