Genetic Variant THSD7A:p.Ala578Ala (chr7-11541507-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_015204.3(THSD7A):c.1734A>G(p.Ala578Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 1,613,206 control chromosomes in the GnomAD database, including 150,358 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 0.44 ( 14508 hom., cov: 32)

Exomes 𝑓: 0.43 ( 135850 hom. )

Consequence

THSD7A
NM_015204.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.467

Publications

16 publications found

Variant links:

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]

THSD7A links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP7

Synonymous conserved (PhyloP=0.467 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THSD7A	NM_015204.3 link	c.1734A>G	p.Ala578Ala	synonymous_variant	Exon 6 of 28	ENST00000423059.9	NP_056019.1	Q9UPZ6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THSD7A	ENST00000423059.9 link	c.1734A>G	p.Ala578Ala	synonymous_variant	Exon 6 of 28	5	NM_015204.3	ENSP00000406482.2		Q9UPZ6
THSD7A	ENST00000497575.1 link	n.223A>G		non_coding_transcript_exon_variant	Exon 2 of 4	5

Frequencies

GnomAD3 genomes

AF:

0.435

AC:

66047

AN:

151798

Hom.:

14497

Cov.:

show subpopulations

Gnomad AFR

AF:

0.474

Gnomad AMI

AF:

0.394

Gnomad AMR

AF:

0.387

Gnomad ASJ

AF:

0.466

Gnomad EAS

AF:

0.517

Gnomad SAS

AF:

0.489

Gnomad FIN

AF:

0.331

Gnomad MID

AF:

0.560

Gnomad NFE

AF:

0.427

Gnomad OTH

AF:

0.431

GnomAD2 exomes

AF:

0.425

AC:

105756

AN:

248892

AF XY:

0.430

show subpopulations

Gnomad AFR exome

AF:

0.482

Gnomad AMR exome

AF:

0.369

Gnomad ASJ exome

AF:

0.467

Gnomad EAS exome

AF:

0.505

Gnomad FIN exome

AF:

0.332

Gnomad NFE exome

AF:

0.419

Gnomad OTH exome

AF:

0.438

GnomAD4 exome

AF:

0.429

AC:

626991

AN:

1461290

Hom.:

135850

Cov.:

AF XY:

0.431

AC XY:

313608

AN XY:

726944

show subpopulations

African (AFR)

AF:

0.484

AC:

16209

AN:

33478

American (AMR)

AF:

0.373

AC:

16664

AN:

44688

Ashkenazi Jewish (ASJ)

AF:

0.476

AC:

12430

AN:

26132

East Asian (EAS)

AF:

0.492

AC:

19526

AN:

39698

South Asian (SAS)

AF:

0.484

AC:

41738

AN:

86240

European-Finnish (FIN)

AF:

0.338

AC:

18025

AN:

53398

Middle Eastern (MID)

AF:

0.502

AC:

2894

AN:

5766

European-Non Finnish (NFE)

AF:

0.425

AC:

472565

AN:

1111538

Other (OTH)

AF:

0.446

AC:

26940

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

19191

38382

57573

76764

95955

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14612

29224

43836

58448

73060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.435

AC:

66092

AN:

151916

Hom.:

14508

Cov.:

AF XY:

0.433

AC XY:

32158

AN XY:

74264

show subpopulations

African (AFR)

AF:

0.474

AC:

19655

AN:

41442

American (AMR)

AF:

0.386

AC:

5900

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.466

AC:

1616

AN:

3468

East Asian (EAS)

AF:

0.517

AC:

2653

AN:

5134

South Asian (SAS)

AF:

0.489

AC:

2358

AN:

4820

European-Finnish (FIN)

AF:

0.331

AC:

3492

AN:

10554

Middle Eastern (MID)

AF:

0.568

AC:

167

AN:

294

European-Non Finnish (NFE)

AF:

0.427

AC:

28981

AN:

67894

Other (OTH)

AF:

0.431

AC:

911

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1920

3839

5759

7678

9598

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

620

1240

1860

2480

3100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.431

Hom.:

21591

Bravo

AF:

0.438

Asia WGS

AF:

0.458

AC:

1595

AN:

3478

EpiCase

AF:

0.430

EpiControl

AF:

0.429

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

2.4

(source)

DANN

Benign

0.60

PhyloP100

0.47

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over