chr15-71279710-A-G

Variant names:

• chr15-71279710-A-G
• rs2994
• NM_024817.3:c.1015+22995A>G

Variant summary

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

The NM_024817.3(THSD4):​c.1015+22995A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 151,762 control chromosomes in the GnomAD database, including 14,501 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 0.42 (14501 hom., cov: 31)
• Consequence: THSD4 NM_024817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.258
• Publications: 6 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

ENSG00000297029 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THSD4	NM_024817.3	c.1015+22995A>G		intron_variant	Intron 6 of 17	ENST00000261862.8	NP_079093.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THSD4	ENST00000261862.8	c.1015+22995A>G		intron_variant	Intron 6 of 17	5	NM_024817.3	ENSP00000261862.8
ENSG00000297029	ENST00000744765.1	n.277T>C		non_coding_transcript_exon_variant	Exon 2 of 2
THSD4	ENST00000355327.7	c.1015+22995A>G		intron_variant	Intron 6 of 17	5		ENSP00000347484.3

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64457 AN: 151644 Hom.: 14486 Cov.: 31

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.498

Gnomad EAS AF: 0.287

Gnomad SAS AF: 0.459

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.500

Gnomad OTH AF: 0.476

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

GnomAD4 genome AF: 0.425 AC: 64493 AN: 151762 Hom.: 14501 Cov.: 31 AF XY: 0.422 AC XY: 31260 AN XY: 74126

African (AFR) AF: 0.317 AC: 13145 AN: 41406

American (AMR) AF: 0.374 AC: 5706 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.498 AC: 1722 AN: 3460

East Asian (EAS) AF: 0.286 AC: 1474 AN: 5150

South Asian (SAS) AF: 0.459 AC: 2199 AN: 4788

European-Finnish (FIN) AF: 0.438 AC: 4603 AN: 10506

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.500 AC: 33972 AN: 67896

Other (OTH) AF: 0.482 AC: 1014 AN: 2102

Alfa AF: 0.481 Hom.: 23208

Bravo AF: 0.414

Asia WGS AF: 0.377 AC: 1315 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.4
DANN	Benign	0.45
PhyloP100		0.26
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: rs2994; hg19: chr15-71572049;