rs11635579

Variant names:

• chr15-71498009-A-C
• rs11635579
• NM_024817.3:c.1152+86186A>C

Your query was ambiguous. Multiple possible variants found:

• chr15-71498009-A-C
• chr15-71498009-A-G
• chr15-71498009-A-T

Variant summary

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

The NM_024817.3(THSD4):​c.1152+86186A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 152,102 control chromosomes in the GnomAD database, including 16,781 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 0.43 (16781 hom., cov: 32)
• Consequence: THSD4 NM_024817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.547
• 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

LOC107984716 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.759 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THSD4	NM_024817.3	MANE Select	c.1152+86186A>C		intron	N/A	NP_079093.2
	THSD4	NM_001394532.1		c.1152+86186A>C		intron	N/A	NP_001381461.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THSD4	ENST00000261862.8	TSL:5 MANE Select	c.1152+86186A>C		intron	N/A	ENSP00000261862.8
	THSD4	ENST00000355327.7	TSL:5	c.1152+86186A>C		intron	N/A	ENSP00000347484.3

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64981 AN: 151984 Hom.: 16774 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.567

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.780

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.456

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

GnomAD4 genome AF: 0.427 AC: 64993 AN: 152102 Hom.: 16781 Cov.: 32 AF XY: 0.436 AC XY: 32375 AN XY: 74338

African (AFR) AF: 0.127 AC: 5290 AN: 41510

American (AMR) AF: 0.567 AC: 8672 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.481 AC: 1668 AN: 3470

East Asian (EAS) AF: 0.779 AC: 4025 AN: 5166

South Asian (SAS) AF: 0.542 AC: 2617 AN: 4828

European-Finnish (FIN) AF: 0.540 AC: 5692 AN: 10538

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.520 AC: 35358 AN: 67984

Other (OTH) AF: 0.462 AC: 978 AN: 2116

Alfa AF: 0.484 Hom.: 55506

Bravo AF: 0.418

Asia WGS AF: 0.654 AC: 2275 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.4
DANN	Benign	0.72
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: rs11635579; hg19: chr15-71790348;