7-11407674-A-G

Variant names:

• chr7-11407674-A-G
• rs6975177
• NM_015204.3:c.3799-251T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015204.3(THSD7A):​c.3799-251T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 152,068 control chromosomes in the GnomAD database, including 12,023 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 0.39 (12023 hom., cov: 32)
• Consequence: THSD7A NM_015204.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0380
• Publications: 2 publications found

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]

ENSG00000230435 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THSD7A	NM_015204.3	c.3799-251T>C		intron_variant	Intron 19 of 27	ENST00000423059.9	NP_056019.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THSD7A	ENST00000423059.9	c.3799-251T>C		intron_variant	Intron 19 of 27	5	NM_015204.3	ENSP00000406482.2
ENSG00000230435	ENST00000425837.1	n.212+508A>G		intron_variant	Intron 1 of 2	4
ENSG00000230333	ENST00000445839.5	n.441+23766A>G		intron_variant	Intron 3 of 3	4

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59553 AN: 151950 Hom.: 12009 Cov.: 32

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.392 AC: 59608 AN: 152068 Hom.: 12023 Cov.: 32 AF XY: 0.390 AC XY: 28975 AN XY: 74342

African (AFR) AF: 0.479 AC: 19887 AN: 41486

American (AMR) AF: 0.417 AC: 6371 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 946 AN: 3472

East Asian (EAS) AF: 0.244 AC: 1262 AN: 5178

South Asian (SAS) AF: 0.176 AC: 850 AN: 4824

European-Finnish (FIN) AF: 0.393 AC: 4147 AN: 10560

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.365 AC: 24812 AN: 67972

Other (OTH) AF: 0.377 AC: 795 AN: 2106

Alfa AF: 0.342 Hom.: 5407

Bravo AF: 0.402

Asia WGS AF: 0.240 AC: 836 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.8
DANN	Benign	0.44
PhyloP100		0.038
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6975177; hg19: chr7-11447301;