chr15-71596534-T-C

Position:

• chr15-71596534-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024817.3(THSD4):​c.1153-63996T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,204 control chromosomes in the GnomAD database, including 984 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 0.11 (984 hom., cov: 33)
• Consequence: THSD4 NM_024817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THSD4	NM_024817.3	c.1153-63996T>C		intron_variant		ENST00000261862.8	NP_079093.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THSD4	ENST00000261862.8	c.1153-63996T>C		intron_variant		5	NM_024817.3	ENSP00000261862.8
THSD4	ENST00000357769.4	c.72+49053T>C		intron_variant		1		ENSP00000350413.4
THSD4	ENST00000355327.7	c.1153-63996T>C		intron_variant		5		ENSP00000347484.3
THSD4	ENST00000567745.5	n.254+49053T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16636 AN: 152088 Hom.: 977 Cov.: 33

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.0890

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.0547

Gnomad EAS AF: 0.0590

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.0772

Gnomad MID AF: 0.0892

Gnomad NFE AF: 0.0936

Gnomad OTH AF: 0.0985

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

GnomAD4 genome AF: 0.110 AC: 16677 AN: 152204 Hom.: 984 Cov.: 33 AF XY: 0.109 AC XY: 8149 AN XY: 74440

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.132

Gnomad4 ASJ AF: 0.0547

Gnomad4 EAS AF: 0.0587

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.0772

Gnomad4 NFE AF: 0.0936

Gnomad4 OTH AF: 0.102

Alfa AF: 0.0986 Hom.: 464

Bravo AF: 0.111

Asia WGS AF: 0.134 AC: 468 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	6.9
DANN	Benign	0.60

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: rs4777414; hg19: chr15-71888873;