rs76917273

Variant names:

• chr15-71280615-T-C
• rs76917273
• NM_024817.3:c.1015+23900T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_024817.3(THSD4):​c.1015+23900T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000659 in 136,564 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000066 (0 hom., cov: 30)
• Consequence: THSD4 NM_024817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.79

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]

LOC124903521 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0000659 (9/136564) while in subpopulation EAS AF= 0.000981 (5/5096). AF 95% confidence interval is 0.000386. There are 0 homozygotes in gnomad4. There are 7 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THSD4	NM_024817.3	c.1015+23900T>C		intron_variant	Intron 6 of 17	ENST00000261862.8	NP_079093.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THSD4	ENST00000261862.8	c.1015+23900T>C		intron_variant	Intron 6 of 17	5	NM_024817.3	ENSP00000261862.8
THSD4	ENST00000355327.7	c.1015+23900T>C		intron_variant	Intron 6 of 17	5		ENSP00000347484.3

Frequencies

GnomAD3 genomes AF: 0.0000659 AC: 9 AN: 136478 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000985

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000706

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000979

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000659 AC: 9 AN: 136564 Hom.: 0 Cov.: 30 AF XY: 0.000105 AC XY: 7 AN XY: 66938

Gnomad4 AFR AF: 0.0000982

Gnomad4 AMR AF: 0.0000705

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000981

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00126 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.0
DANN	Benign	0.45

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: rs76917273; hg19: chr15-71572954; COSMIC: COSV55978050;