rs9806183

Variant names:

• chr15-71282460-G-A
• rs9806183
• NM_024817.3:c.1015+25745G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-71282460-G-A
• chr15-71282460-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_024817.3(THSD4):​c.1015+25745G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00404 in 145,038 control chromosomes in the GnomAD database, including 3 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 0.0040 (3 hom., cov: 31)
• Consequence: THSD4 NM_024817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.129
• Publications: 4 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: Franklin by Genoox, Ambry Genetics

LOC124903521 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00404 (586/145038) while in subpopulation AFR AF = 0.0148 (564/38074). AF 95% confidence interval is 0.0138. There are 3 homozygotes in GnomAd4. There are 263 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 586 AD gene.

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.1015+25745G>A		intron	N/A	NP_079093.2	Q6ZMP0-1
	THSD4	NM_001394532.1		c.1015+25745G>A		intron	N/A	NP_001381461.1	Q6ZMP0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THSD4	ENST00000261862.8	TSL:5 MANE Select	c.1015+25745G>A		intron	N/A	ENSP00000261862.8	Q6ZMP0-1
	THSD4	ENST00000355327.7	TSL:5	c.1015+25745G>A		intron	N/A	ENSP00000347484.3	Q6ZMP0-1
	ENSG00000297029	ENST00000744765.1		n.207-2680C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00402 AC: 582 AN: 144912 Hom.: 3 Cov.: 31

Gnomad AFR AF: 0.0148

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00107

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: 0.0000300

Gnomad OTH AF: 0.00252

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

GnomAD4 genome AF: 0.00404 AC: 586 AN: 145038 Hom.: 3 Cov.: 31 AF XY: 0.00372 AC XY: 263 AN XY: 70636

African (AFR) AF: 0.0148 AC: 564 AN: 38074

American (AMR) AF: 0.00107 AC: 15 AN: 14042

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3384

East Asian (EAS) AF: 0.00 AC: 0 AN: 5144

South Asian (SAS) AF: 0.00 AC: 0 AN: 4440

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10188

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 282

European-Non Finnish (NFE) AF: 0.0000300 AC: 2 AN: 66592

Other (OTH) AF: 0.00249 AC: 5 AN: 2008

Alfa AF: 0.00 Hom.: 1670

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.56
DANN	Benign	0.21
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism

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: rs9806183; hg19: chr15-71574799;