NM_015204.3:c.1822+3421G>A

Variant names:

• chr7-11537998-C-T
• rs53
• NM_015204.3:c.1822+3421G>A

Variant summary

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

The NM_015204.3(THSD7A):​c.1822+3421G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,134 control chromosomes in the GnomAD database, including 3,608 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 0.19 (3608 hom., cov: 32)
• Consequence: THSD7A NM_015204.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.59
• Publications: 0 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015204.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THSD7A	NM_015204.3	MANE Select	c.1822+3421G>A		intron	N/A	NP_056019.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THSD7A	ENST00000423059.9	TSL:5 MANE Select	c.1822+3421G>A		intron	N/A	ENSP00000406482.2
	THSD7A	ENST00000497575.1	TSL:5	n.311+3421G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29093 AN: 152016 Hom.: 3603 Cov.: 32

Gnomad AFR AF: 0.0517

Gnomad AMI AF: 0.0791

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.191 AC: 29097 AN: 152134 Hom.: 3608 Cov.: 32 AF XY: 0.193 AC XY: 14386 AN XY: 74376

African (AFR) AF: 0.0515 AC: 2140 AN: 41536

American (AMR) AF: 0.390 AC: 5949 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 838 AN: 3466

East Asian (EAS) AF: 0.188 AC: 969 AN: 5162

South Asian (SAS) AF: 0.135 AC: 649 AN: 4820

European-Finnish (FIN) AF: 0.227 AC: 2399 AN: 10582

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.229 AC: 15567 AN: 67982

Other (OTH) AF: 0.219 AC: 462 AN: 2112

Alfa AF: 0.221 Hom.: 12613

Bravo AF: 0.199

Asia WGS AF: 0.164 AC: 572 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.10
DANN	Benign	0.49
PhyloP100		-5.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs53; hg19: chr7-11577625;