rs12912888

Variant names:

• chr15-71564345-G-A
• rs12912888
• NM_024817.3:c.1153-96185G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-71564345-G-A
• chr15-71564345-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.1153-96185G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.833 in 152,144 control chromosomes in the GnomAD database, including 53,240 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 0.83 (53240 hom., cov: 32)
• Consequence: THSD4 NM_024817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.120
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.869 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.1153-96185G>A		intron	N/A	NP_079093.2	Q6ZMP0-1
	THSD4	NM_001394532.1		c.1153-96185G>A		intron	N/A	NP_001381461.1	Q6ZMP0-1
	THSD4	NM_001286429.2		c.72+16864G>A		intron	N/A	NP_001273358.1	Q6ZMP0-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THSD4	ENST00000261862.8	TSL:5 MANE Select	c.1153-96185G>A		intron	N/A	ENSP00000261862.8	Q6ZMP0-1
	THSD4	ENST00000357769.4	TSL:1	c.72+16864G>A		intron	N/A	ENSP00000350413.4	Q6ZMP0-4
	THSD4	ENST00000355327.7	TSL:5	c.1153-96185G>A		intron	N/A	ENSP00000347484.3	Q6ZMP0-1

Frequencies

GnomAD3 genomes AF: 0.833 AC: 126622 AN: 152026 Hom.: 53222 Cov.: 32

Gnomad AFR AF: 0.846

Gnomad AMI AF: 0.867

Gnomad AMR AF: 0.761

Gnomad ASJ AF: 0.909

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.685

Gnomad FIN AF: 0.809

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.875

Gnomad OTH AF: 0.838

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

GnomAD4 genome AF: 0.833 AC: 126687 AN: 152144 Hom.: 53240 Cov.: 32 AF XY: 0.823 AC XY: 61212 AN XY: 74362

African (AFR) AF: 0.846 AC: 35092 AN: 41490

American (AMR) AF: 0.761 AC: 11628 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.909 AC: 3155 AN: 3472

East Asian (EAS) AF: 0.509 AC: 2628 AN: 5168

South Asian (SAS) AF: 0.685 AC: 3301 AN: 4818

European-Finnish (FIN) AF: 0.809 AC: 8570 AN: 10590

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.875 AC: 59515 AN: 68012

Other (OTH) AF: 0.836 AC: 1763 AN: 2110

Alfa AF: 0.832 Hom.: 16682

Bravo AF: 0.833

Asia WGS AF: 0.613 AC: 2134 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.4
DANN	Benign	0.34
PhyloP100		-0.12
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: rs12912888; hg19: chr15-71856684;