NM_024817.3:c.1016-49224A>G

Variant names:

• chr15-71362463-A-G
• rs10518954
• NM_024817.3:c.1016-49224A>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.1016-49224A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,148 control chromosomes in the GnomAD database, including 3,789 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 0.20 (3789 hom., cov: 32)
• Consequence: THSD4 NM_024817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.289
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.527 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.1016-49224A>G		intron	N/A	NP_079093.2
	THSD4	NM_001394532.1		c.1016-49224A>G		intron	N/A	NP_001381461.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THSD4	ENST00000261862.8	TSL:5 MANE Select	c.1016-49224A>G		intron	N/A	ENSP00000261862.8
	THSD4	ENST00000355327.7	TSL:5	c.1016-49224A>G		intron	N/A	ENSP00000347484.3

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29836 AN: 152030 Hom.: 3789 Cov.: 32

Gnomad AFR AF: 0.0715

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.543

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.196 AC: 29839 AN: 152148 Hom.: 3789 Cov.: 32 AF XY: 0.201 AC XY: 14974 AN XY: 74368

African (AFR) AF: 0.0716 AC: 2975 AN: 41552

American (AMR) AF: 0.276 AC: 4222 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 549 AN: 3470

East Asian (EAS) AF: 0.543 AC: 2796 AN: 5146

South Asian (SAS) AF: 0.254 AC: 1223 AN: 4816

European-Finnish (FIN) AF: 0.260 AC: 2755 AN: 10582

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14742 AN: 67988

Other (OTH) AF: 0.181 AC: 383 AN: 2114

Alfa AF: 0.199 Hom.: 454

Bravo AF: 0.195

Asia WGS AF: 0.322 AC: 1120 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.5
DANN	Benign	0.74
PhyloP100		0.29
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: rs10518954; hg19: chr15-71654802;