rs6494967

Positions:

• chr15-71774622-G-A
• chr15-71774622-G-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
THSD4	NM_024817.3	c.2915-2610G>A		intron_variant		ENST00000261862.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THSD4	ENST00000261862.8	c.2915-2610G>A		intron_variant		5	NM_024817.3	P1
THSD4	ENST00000357769.4	c.1835-2610G>A		intron_variant		1
THSD4	ENST00000355327.7	c.2915-2610G>A		intron_variant		5		P1

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

Gnomad4 AFR AF: 0.820

Gnomad4 AMR AF: 0.786

Gnomad4 ASJ AF: 0.676

Gnomad4 EAS AF: 0.397

Gnomad4 SAS AF: 0.590

Gnomad4 FIN AF: 0.740

Gnomad4 NFE AF: 0.707

Gnomad4 OTH AF: 0.726

Alfa AF: 0.707 Hom.: 59592

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs6494967; hg19: chr15-72066961;