2-136957689-T-C

Position:

• chr2-136957689-T-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+75372T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 151,932 control chromosomes in the GnomAD database, including 18,757 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 0.48 (18757 hom., cov: 32)
• Consequence: THSD7B NM_001316349.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30

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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THSD7B	NM_001316349.2	c.139+75372T>C		intron_variant		ENST00000409968.6
THSD7B	XM_047445935.1	c.-285+51123T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THSD7B	ENST00000409968.6	c.139+75372T>C		intron_variant		5	NM_001316349.2	P1
THSD7B	ENST00000472720.5	c.*105+51123T>C		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.481 AC: 73060 AN: 151814 Hom.: 18763 Cov.: 32

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.659

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.636

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.580

Gnomad OTH AF: 0.458

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

GnomAD4 genome AF: 0.481 AC: 73080 AN: 151932 Hom.: 18757 Cov.: 32 AF XY: 0.479 AC XY: 35565 AN XY: 74258

Gnomad4 AFR AF: 0.352

Gnomad4 AMR AF: 0.403

Gnomad4 ASJ AF: 0.520

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.378

Gnomad4 FIN AF: 0.636

Gnomad4 NFE AF: 0.580

Gnomad4 OTH AF: 0.454

Alfa AF: 0.508 Hom.: 3439

Bravo AF: 0.458

Asia WGS AF: 0.268 AC: 931 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.21
DANN	Benign	0.47

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: rs524398; hg19: chr2-137715259;