Variant chr15-71111256-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001394532.1(THSD4):c.-80+14250T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00288 in 1,613,972 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0025 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0029 ( 9 hom. )

Consequence

THSD4
NM_001394532.1 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.966

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:

CT62 (HGNC:):

CT62 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 (BayesDel_noAF=-0.83).

BP6

Variant 15-71111256-T-C is Benign according to our data. Variant chr15-71111256-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2645498.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00249 (379/152338) while in subpopulation AMR AF= 0.00993 (152/15304). AF 95% confidence interval is 0.00864. There are 3 homozygotes in gnomad4. There are 168 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 379 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	Protein
THSD4	NM_001394532.1 linkuse as main transcript	c.-80+14250T>C	intron_variant		NP_001381461.1
CT62	NR_168259.1 linkuse as main transcript	n.823A>G	non_coding_transcript_exon_variant	4/4
CT62	NR_168260.1 linkuse as main transcript	n.1032A>G	non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	Protein	UniProt
THSD4	ENST00000355327.7 linkuse as main transcript	c.-80+14250T>C	intron_variant		5	ENSP00000347484.3	Q6ZMP0-1
CT62	ENST00000564862.2 linkuse as main transcript	n.171A>G	non_coding_transcript_exon_variant	1/2	2
CT62	ENST00000566432.1 linkuse as main transcript	n.1810A>G	non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.00249

AC:

379

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00995

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00273

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00249

AC:

621

AN:

249234

Hom.:

AF XY:

0.00224

AC XY:

303

AN XY:

135208

show subpopulations

Gnomad AFR exome

AF:

0.000517

Gnomad AMR exome

AF:

0.00611

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000511

Gnomad NFE exome

AF:

0.00318

Gnomad OTH exome

AF:

0.00529

GnomAD4 exome

AF:

0.00292

AC:

4264

AN:

1461634

Hom.:

Cov.:

AF XY:

0.00276

AC XY:

2009

AN XY:

727094

show subpopulations

Gnomad4 AFR exome

AF:

0.000657

Gnomad4 AMR exome

AF:

0.00657

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.000300

Gnomad4 NFE exome

AF:

0.00336

Gnomad4 OTH exome

AF:

0.00325

GnomAD4 genome

AF:

0.00249

AC:

379

AN:

152338

Hom.:

Cov.:

AF XY:

0.00226

AC XY:

168

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.000721

Gnomad4 AMR

AF:

0.00993

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00273

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00217

Hom.:

Bravo

AF:

0.00318

EpiCase

AF:

0.00294

EpiControl

AF:

0.00320

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2024

CT62: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.4

DANN

Benign

0.88

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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