NM_015204.3:c.4560G>A

Variant names:

• chr7-11379660-C-T
• rs17164530
• NM_015204.3:c.4560G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BS1 BS2

The NM_015204.3(THSD7A):​c.4560G>A​(p.Pro1520Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00172 in 1,592,152 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0076 (13 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (17 hom.)
• Consequence: THSD7A NM_015204.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.57
• Publications: 3 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]

ENSG00000230333 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 7-11379660-C-T is Benign according to our data. Variant chr7-11379660-C-T is described in ClinVar as Benign. ClinVar VariationId is 776208.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.57 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00758 (1155/152278) while in subpopulation AFR AF = 0.0254 (1057/41562). AF 95% confidence interval is 0.0242. There are 13 homozygotes in GnomAd4. There are 550 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 13 gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THSD7A	NM_015204.3	MANE Select	c.4560G>A	p.Pro1520Pro	synonymous	Exon 25 of 28	NP_056019.1	Q9UPZ6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THSD7A	ENST00000423059.9	TSL:5 MANE Select	c.4560G>A	p.Pro1520Pro	synonymous	Exon 25 of 28	ENSP00000406482.2	Q9UPZ6
	THSD7A	ENST00000408005.2	TSL:1	n.96G>A		non_coding_transcript_exon	Exon 1 of 4
	ENSG00000230333	ENST00000421121.5	TSL:1	n.196+291C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00758 AC: 1153 AN: 152160 Hom.: 13 Cov.: 33

Gnomad AFR AF: 0.0255

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00314

Gnomad ASJ AF: 0.00835

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00383

GnomAD2 exomes AF: 0.00196 AC: 427 AN: 217632 AF XY: 0.00149

Gnomad AFR exome AF: 0.0224

Gnomad AMR exome AF: 0.00131

Gnomad ASJ exome AF: 0.00579

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000312

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00110 AC: 1577 AN: 1439874 Hom.: 17 Cov.: 31 AF XY: 0.000986 AC XY: 704 AN XY: 713778

African (AFR) AF: 0.0264 AC: 871 AN: 33054

American (AMR) AF: 0.00141 AC: 59 AN: 41938

Ashkenazi Jewish (ASJ) AF: 0.00698 AC: 179 AN: 25630

East Asian (EAS) AF: 0.00 AC: 0 AN: 38734

South Asian (SAS) AF: 0.000242 AC: 20 AN: 82490

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52040

Middle Eastern (MID) AF: 0.00488 AC: 28 AN: 5738

European-Non Finnish (NFE) AF: 0.000220 AC: 242 AN: 1100636

Other (OTH) AF: 0.00299 AC: 178 AN: 59614

GnomAD4 genome AF: 0.00758 AC: 1155 AN: 152278 Hom.: 13 Cov.: 33 AF XY: 0.00739 AC XY: 550 AN XY: 74452

African (AFR) AF: 0.0254 AC: 1057 AN: 41562

American (AMR) AF: 0.00314 AC: 48 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00835 AC: 29 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68030

Other (OTH) AF: 0.00379 AC: 8 AN: 2112

Alfa AF: 0.00406 Hom.: 5

Bravo AF: 0.00824

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	11
DANN	Benign	0.84
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs17164530; hg19: chr7-11419287;