15-71215182-C-G

Position:

chr15-71215182-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_024817.3(THSD4):c.247C>G(p.Arg83Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000886 in 1,365,162 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000088 ( 0 hom. )

Consequence

THSD4
NM_024817.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0260

Variant links:

Genes affected

THSD4 (HGNC:25835): (thrombospondin type 1 domain containing 4) Predicted to enable hydrolase activity. Predicted to be an extracellular matrix structural constituent. Predicted to act upstream of or within elastic fiber assembly. Located in collagen-containing extracellular matrix and extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

THSD4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02810049).

BP6

Variant 15-71215182-C-G is Benign according to our data. Variant chr15-71215182-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3177168.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0000924 (14/151512) while in subpopulation NFE AF= 0.000162 (11/67824). AF 95% confidence interval is 0.0000907. There are 0 homozygotes in gnomad4. There are 9 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
THSD4	NM_024817.3 linkuse as main transcript	c.247C>G	p.Arg83Gly	missense_variant	4/18	ENST00000261862.8
THSD4	NM_001394532.1 linkuse as main transcript	c.247C>G	p.Arg83Gly	missense_variant	4/18
THSD4	XM_047433080.1 linkuse as main transcript	c.247C>G	p.Arg83Gly	missense_variant	4/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THSD4	ENST00000261862.8 linkuse as main transcript	c.247C>G	p.Arg83Gly	missense_variant	4/18	5	NM_024817.3	P1	Q6ZMP0-1
THSD4	ENST00000355327.7 linkuse as main transcript	c.247C>G	p.Arg83Gly	missense_variant	4/18	5		P1	Q6ZMP0-1
THSD4	ENST00000620694.1 linkuse as main transcript	c.247C>G	p.Arg83Gly	missense_variant	4/4	3

Frequencies

GnomAD3 genomes

AF:

0.0000924

AC:

AN:

151512

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000565

AC:

AN:

35368

Hom.:

AF XY:

0.0000463

AC XY:

AN XY:

21610

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000143

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000882

AC:

107

AN:

1213650

Hom.:

Cov.:

AF XY:

0.0000858

AC XY:

AN XY:

594316

show subpopulations

Gnomad4 AFR exome

AF:

0.0000418

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000110

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000105

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000924

AC:

AN:

151512

Hom.:

Cov.:

AF XY:

0.000122

AC XY:

AN XY:

73970

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000132

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.0000855

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 14, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.048

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.73

CADD

Benign

8.2

DANN

Benign

0.67

DEOGEN2

Benign

0.013

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0077

LIST_S2

Benign

0.41

T;T

M_CAP

Benign

0.039

MetaRNN

Benign

0.028

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.14

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.72

PROVEAN

Benign

0.12

N;.

REVEL

Benign

0.021

Sift

Benign

0.43

T;.

Sift4G

Benign

0.44

T;T

Polyphen

0.0

B;.

Vest4

0.096

MutPred

0.26

Loss of MoRF binding (P = 0.0286);Loss of MoRF binding (P = 0.0286);

MVP

0.048

MPC

0.15

ClinPred

0.031

GERP RS

-1.4

Varity_R

0.082

gMVP

0.25

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

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