7-11519953-T-C

Position:

• chr7-11519953-T-C

Variant summary

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

The NM_015204.3(THSD7A):​c.1822+21466A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,010 control chromosomes in the GnomAD database, including 3,504 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 0.21 (3504 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: THSD7A NM_015204.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24

Genes affected

THSD7A (HGNC:22207): (thrombospondin type 1 domain containing 7A) The protein encoded by this gene is found almost exclusively in endothelial cells from placenta and umbilical cord. The encoded protein appears to interact with alpha(V)beta(3) integrin and paxillin to inhibit endothelial cell migration and tube formation. This protein may be involved in cytoskeletal organization. Variations in this gene may be associated with low bone mineral density in osteoporosis. [provided by RefSeq, Aug 2010]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THSD7A	NM_015204.3	c.1822+21466A>G		intron_variant		ENST00000423059.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THSD7A	ENST00000423059.9	c.1822+21466A>G		intron_variant		5	NM_015204.3	P1
	ENST00000445839.5	n.442-99T>C		intron_variant, non_coding_transcript_variant		4
THSD7A	ENST00000497575.1	n.311+21466A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31654 AN: 151884 Hom.: 3498 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.183

GnomAD4 exome AF: 0.500 AC: 2 AN: 4 Hom.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.208 AC: 31693 AN: 152006 Hom.: 3504 Cov.: 32 AF XY: 0.211 AC XY: 15694 AN XY: 74324

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.180

Gnomad4 OTH AF: 0.183

Alfa AF: 0.186 Hom.: 1267

Bravo AF: 0.208

Asia WGS AF: 0.179 AC: 622 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.6
DANN	Benign	0.38

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: rs10277665; hg19: chr7-11559580;