rs6494967

Variant names:

• chr15-71774622-G-A
• rs6494967
• NM_024817.3:c.2915-2610G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-71774622-G-A
• chr15-71774622-G-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.2915-2610G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.732 in 151,836 control chromosomes in the GnomAD database, including 41,416 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 0.73 (41416 hom., cov: 29)
• Consequence: THSD4 NM_024817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.198
• 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: 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THSD4	NM_024817.3	c.2915-2610G>A		intron_variant	Intron 17 of 17	ENST00000261862.8	NP_079093.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THSD4	ENST00000261862.8	c.2915-2610G>A		intron_variant	Intron 17 of 17	5	NM_024817.3	ENSP00000261862.8
THSD4	ENST00000357769.4	c.1835-2610G>A		intron_variant	Intron 11 of 11	1		ENSP00000350413.4
THSD4	ENST00000355327.7	c.2915-2610G>A		intron_variant	Intron 17 of 17	5		ENSP00000347484.3

Frequencies

GnomAD3 genomes AF: 0.732 AC: 111095 AN: 151718 Hom.: 41361 Cov.: 29

Gnomad AFR AF: 0.820

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.785

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.740

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.707

Gnomad OTH AF: 0.727

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

GnomAD4 genome AF: 0.732 AC: 111214 AN: 151836 Hom.: 41416 Cov.: 29 AF XY: 0.728 AC XY: 54029 AN XY: 74210

African (AFR) AF: 0.820 AC: 33951 AN: 41398

American (AMR) AF: 0.786 AC: 11976 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.676 AC: 2344 AN: 3468

East Asian (EAS) AF: 0.397 AC: 2041 AN: 5142

South Asian (SAS) AF: 0.590 AC: 2832 AN: 4804

European-Finnish (FIN) AF: 0.740 AC: 7785 AN: 10522

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.707 AC: 48037 AN: 67948

Other (OTH) AF: 0.726 AC: 1527 AN: 2104

Alfa AF: 0.712 Hom.: 146580

Bravo AF: 0.741

Asia WGS AF: 0.504 AC: 1755 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.74
DANN	Benign	0.24
PhyloP100		-0.20
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: rs6494967; hg19: chr15-72066961;