rs518614

chr2-136959281-G-C

Variant summary

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

The NM_001316349.2(THSD7B):c.139+76964G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 152,066 control chromosomes in the GnomAD database, including 14,817 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 0.41 (14817 hom., cov: 32)
• Consequence: THSD7B NM_001316349.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550

Genes affected

THSD7B (HGNC:29348): (thrombospondin type 1 domain containing 7B) Predicted to be involved in actin cytoskeleton reorganization. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THSD7B	NM_001316349.2	c.139+76964G>C		intron_variant		ENST00000409968.6
THSD7B	XM_047445935.1	c.-285+52715G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THSD7B	ENST00000409968.6	c.139+76964G>C		intron_variant		5	NM_001316349.2	P1
THSD7B	ENST00000472720.5	c.*105+52715G>C		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61963 AN: 151948 Hom.: 14822 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.654

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.0694

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.561

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.549

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.407 AC: 61958 AN: 152066 Hom.: 14817 Cov.: 32 AF XY: 0.404 AC XY: 30008 AN XY: 74328

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.361

Gnomad4 ASJ AF: 0.507

Gnomad4 EAS AF: 0.0696

Gnomad4 SAS AF: 0.317

Gnomad4 FIN AF: 0.561

Gnomad4 NFE AF: 0.549

Gnomad4 OTH AF: 0.391

Alfa AF: 0.475 Hom.: 2299

Bravo AF: 0.381

Asia WGS AF: 0.181 AC: 632 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.5
Dann	Benign	0.51

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: rs518614; hg19: chr2-137716851;