NM_024817.3:c.-79-9779T>C

Variant names:

• chr15-71131670-T-C
• rs12904863
• NM_024817.3:c.-79-9779T>C

Variant summary

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

The NM_024817.3(THSD4):​c.-79-9779T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,174 control chromosomes in the GnomAD database, including 1,145 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 0.10 (1145 hom., cov: 32)
• Consequence: THSD4 NM_024817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.995
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024817.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THSD4	NM_024817.3	MANE Select	c.-79-9779T>C		intron	N/A	NP_079093.2
	THSD4	NM_001394532.1		c.-79-9779T>C		intron	N/A	NP_001381461.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THSD4	ENST00000261862.8	TSL:5 MANE Select	c.-79-9779T>C		intron	N/A	ENSP00000261862.8
	THSD4	ENST00000355327.7	TSL:5	c.-79-9779T>C		intron	N/A	ENSP00000347484.3
	THSD4	ENST00000620694.1	TSL:3	c.-79-9779T>C		intron	N/A	ENSP00000484438.1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15762 AN: 152058 Hom.: 1142 Cov.: 32

Gnomad AFR AF: 0.0767

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0653

Gnomad ASJ AF: 0.0571

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0971

Gnomad OTH AF: 0.0893

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

GnomAD4 genome AF: 0.104 AC: 15784 AN: 152174 Hom.: 1145 Cov.: 32 AF XY: 0.107 AC XY: 7971 AN XY: 74404

African (AFR) AF: 0.0769 AC: 3193 AN: 41518

American (AMR) AF: 0.0652 AC: 997 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0571 AC: 198 AN: 3468

East Asian (EAS) AF: 0.426 AC: 2195 AN: 5156

South Asian (SAS) AF: 0.186 AC: 898 AN: 4818

European-Finnish (FIN) AF: 0.137 AC: 1452 AN: 10592

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0971 AC: 6603 AN: 68000

Other (OTH) AF: 0.0950 AC: 201 AN: 2116

Alfa AF: 0.0910 Hom.: 368

Bravo AF: 0.0972

Asia WGS AF: 0.288 AC: 1001 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.7
DANN	Benign	0.78
PhyloP100		-0.99
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: rs12904863; hg19: chr15-71424009;