15-71398952-C-G

Variant names:

• chr15-71398952-C-G
• rs1982234
• NM_024817.3:c.1016-12735C>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.1016-12735C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 151,734 control chromosomes in the GnomAD database, including 7,137 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 0.27 (7137 hom., cov: 30)
• Consequence: THSD4 NM_024817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 0 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

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 (NFE) allele frequency at 95% confidence interval = 0.38 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.1016-12735C>G		intron	N/A	NP_079093.2	Q6ZMP0-1
	THSD4	NM_001394532.1		c.1016-12735C>G		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.1016-12735C>G		intron	N/A	ENSP00000261862.8	Q6ZMP0-1
	THSD4	ENST00000355327.7	TSL:5	c.1016-12735C>G		intron	N/A	ENSP00000347484.3	Q6ZMP0-1

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41055 AN: 151616 Hom.: 7139 Cov.: 30

Gnomad AFR AF: 0.0642

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.324

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

GnomAD4 genome AF: 0.270 AC: 41038 AN: 151734 Hom.: 7137 Cov.: 30 AF XY: 0.268 AC XY: 19887 AN XY: 74086

African (AFR) AF: 0.0641 AC: 2653 AN: 41408

American (AMR) AF: 0.257 AC: 3915 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 1610 AN: 3470

East Asian (EAS) AF: 0.165 AC: 846 AN: 5116

South Asian (SAS) AF: 0.242 AC: 1163 AN: 4808

European-Finnish (FIN) AF: 0.336 AC: 3521 AN: 10478

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.383 AC: 26042 AN: 67918

Other (OTH) AF: 0.320 AC: 672 AN: 2098

Alfa AF: 0.208 Hom.: 556

Bravo AF: 0.256

Asia WGS AF: 0.196 AC: 685 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	0.57
DANN	Benign	0.76
PhyloP100		-1.1
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: rs1982234; hg19: chr15-71691291;