Variant 7-11406947-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_015204.3(THSD7A):c.4025G>A(p.Arg1342Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000998 in 1,613,794 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0047 ( 5 hom., cov: 32)

Exomes 𝑓: 0.00061 ( 4 hom. )

Consequence

THSD7A
NM_015204.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.162

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:

ENSG00000230333 (HGNC:):

ENSG00000230333 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0054184496).

BP6

Variant 7-11406947-C-T is Benign according to our data. Variant chr7-11406947-C-T is described in ClinVar as [Benign]. Clinvar id is 781897.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THSD7A	NM_015204.3 link	c.4025G>A	p.Arg1342Gln	missense_variant	Exon 21 of 28	ENST00000423059.9	NP_056019.1	Q9UPZ6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
THSD7A	ENST00000423059.9 link	c.4025G>A	p.Arg1342Gln	missense_variant	Exon 21 of 28	5	NM_015204.3	ENSP00000406482.2	Q9UPZ6
ENSG00000230333	ENST00000445839.5 link	n.441+23039C>T		intron_variant	Intron 3 of 3	4
ENSG00000230435	ENST00000425837.1 link	n.-8C>T		upstream_gene_variant		4

Frequencies

GnomAD3 genomes

AF:

0.00474

AC:

721

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0159

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00807

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00142

AC:

353

AN:

248726

Hom.:

AF XY:

0.00106

AC XY:

143

AN XY:

134942

show subpopulations

Gnomad AFR exome

AF:

0.0159

Gnomad AMR exome

AF:

0.000814

Gnomad ASJ exome

AF:

0.00538

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000142

Gnomad OTH exome

AF:

0.000993

GnomAD4 exome

AF:

0.000608

AC:

889

AN:

1461562

Hom.:

Cov.:

AF XY:

0.000576

AC XY:

419

AN XY:

727054

show subpopulations

Gnomad4 AFR exome

AF:

0.0145

Gnomad4 AMR exome

AF:

0.000895

Gnomad4 ASJ exome

AF:

0.00670

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000549

Gnomad4 OTH exome

AF:

0.00176

GnomAD4 genome

AF:

0.00474

AC:

722

AN:

152232

Hom.:

Cov.:

AF XY:

0.00450

AC XY:

335

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0159

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.00807

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.000954

Hom.:

Bravo

AF:

0.00518

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0122

AC:

ESP6500EA

AF:

0.000721

AC:

ExAC

AF:

0.00161

AC:

195

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 04, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.011

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.74

T;T

MetaRNN

Benign

0.0054

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;.

PrimateAI

Benign

0.19

PROVEAN

Benign

-0.15

N;.

REVEL

Benign

0.066

Sift

Benign

0.44

T;.

Sift4G

Benign

0.50

T;T

Polyphen

0.0010

B;.

Vest4

0.32

MVP

0.068

MPC

0.048

ClinPred

0.0032

GERP RS

-0.66

Varity_R

0.038

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over