7-11642137-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.191-5176A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,176 control chromosomes in the GnomAD database, including 1,832 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 0.15 (1832 hom., cov: 32)
• Consequence: THSD7A NM_015204.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.589

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THSD7A	NM_015204.3	c.191-5176A>G		intron_variant		ENST00000423059.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THSD7A	ENST00000423059.9	c.191-5176A>G		intron_variant		5	NM_015204.3	P1
THSD7A	ENST00000480061.1	n.218-5176A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22417 AN: 152058 Hom.: 1832 Cov.: 32

Gnomad AFR AF: 0.0990

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.0700

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.0621

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.147 AC: 22416 AN: 152176 Hom.: 1832 Cov.: 32 AF XY: 0.147 AC XY: 10907 AN XY: 74380

Gnomad4 AFR AF: 0.0988

Gnomad4 AMR AF: 0.209

Gnomad4 ASJ AF: 0.0700

Gnomad4 EAS AF: 0.173

Gnomad4 SAS AF: 0.0615

Gnomad4 FIN AF: 0.154

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.144

Alfa AF: 0.0895 Hom.: 139

Bravo AF: 0.152

Asia WGS AF: 0.119 AC: 413 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.5
Dann	Benign	0.85

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: rs1358169; hg19: chr7-11681764;