chr15-71596534-T-C

Variant names:

• chr15-71596534-T-C
• rs4777414
• NM_024817.3:c.1153-63996T>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.1153-63996T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,204 control chromosomes in the GnomAD database, including 984 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 0.11 (984 hom., cov: 33)
• Consequence: THSD4 NM_024817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43
• Publications: 2 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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.164 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.1153-63996T>C		intron	N/A	NP_079093.2
	THSD4	NM_001394532.1		c.1153-63996T>C		intron	N/A	NP_001381461.1
	THSD4	NM_001286429.2		c.72+49053T>C		intron	N/A	NP_001273358.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THSD4	ENST00000261862.8	TSL:5 MANE Select	c.1153-63996T>C		intron	N/A	ENSP00000261862.8
	THSD4	ENST00000357769.4	TSL:1	c.72+49053T>C		intron	N/A	ENSP00000350413.4
	THSD4	ENST00000355327.7	TSL:5	c.1153-63996T>C		intron	N/A	ENSP00000347484.3

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16636 AN: 152088 Hom.: 977 Cov.: 33

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.0890

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.0547

Gnomad EAS AF: 0.0590

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.0772

Gnomad MID AF: 0.0892

Gnomad NFE AF: 0.0936

Gnomad OTH AF: 0.0985

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

GnomAD4 genome AF: 0.110 AC: 16677 AN: 152204 Hom.: 984 Cov.: 33 AF XY: 0.109 AC XY: 8149 AN XY: 74440

African (AFR) AF: 0.140 AC: 5829 AN: 41512

American (AMR) AF: 0.132 AC: 2010 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0547 AC: 190 AN: 3472

East Asian (EAS) AF: 0.0587 AC: 305 AN: 5194

South Asian (SAS) AF: 0.174 AC: 838 AN: 4816

European-Finnish (FIN) AF: 0.0772 AC: 819 AN: 10608

Middle Eastern (MID) AF: 0.0856 AC: 25 AN: 292

European-Non Finnish (NFE) AF: 0.0936 AC: 6365 AN: 68006

Other (OTH) AF: 0.102 AC: 215 AN: 2114

Alfa AF: 0.0985 Hom.: 510

Bravo AF: 0.111

Asia WGS AF: 0.134 AC: 468 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	6.9
DANN	Benign	0.60
PhyloP100		1.4
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: rs4777414; hg19: chr15-71888873;