rs1913768

Variant names:

• chr15-71357205-G-A
• rs1913768
• NM_024817.3:c.1016-54482G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024817.3(THSD4):​c.1016-54482G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,170 control chromosomes in the GnomAD database, including 1,533 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 0.14 (1533 hom., cov: 32)
• Consequence: THSD4 NM_024817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.545
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• aortic aneurysm, familial thoracic 12

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• familial thoracic aortic aneurysm and aortic dissection

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Franklin by Genoox

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THSD4	NM_024817.3	c.1016-54482G>A		intron_variant	Intron 6 of 17	ENST00000261862.8	NP_079093.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THSD4	ENST00000261862.8	c.1016-54482G>A		intron_variant	Intron 6 of 17	5	NM_024817.3	ENSP00000261862.8
THSD4	ENST00000355327.7	c.1016-54482G>A		intron_variant	Intron 6 of 17	5		ENSP00000347484.3

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21232 AN: 152052 Hom.: 1530 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.130

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.140 AC: 21241 AN: 152170 Hom.: 1533 Cov.: 32 AF XY: 0.140 AC XY: 10433 AN XY: 74390

African (AFR) AF: 0.112 AC: 4671 AN: 41532

American (AMR) AF: 0.104 AC: 1586 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 504 AN: 3472

East Asian (EAS) AF: 0.102 AC: 525 AN: 5168

South Asian (SAS) AF: 0.200 AC: 964 AN: 4820

European-Finnish (FIN) AF: 0.182 AC: 1929 AN: 10580

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.156 AC: 10579 AN: 67978

Other (OTH) AF: 0.132 AC: 278 AN: 2112

Alfa AF: 0.150 Hom.: 2952

Bravo AF: 0.131

Asia WGS AF: 0.152 AC: 530 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.19
DANN	Benign	0.36
PhyloP100		-0.55
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1913768; hg19: chr15-71649544;