rs4954368

chr2-137000363-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.140-56057T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 151,946 control chromosomes in the GnomAD database, including 6,733 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 0.29 (6733 hom., cov: 32)
• Consequence: THSD7B NM_001316349.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THSD7B	NM_001316349.2	c.140-56057T>C		intron_variant		ENST00000409968.6
THSD7B	XM_047445935.1	c.-284-56057T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THSD7B	ENST00000409968.6	c.140-56057T>C		intron_variant		5	NM_001316349.2	P1
THSD7B	ENST00000472720.5	c.*106-56057T>C		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44513 AN: 151828 Hom.: 6726 Cov.: 32

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.284

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

GnomAD4 genome AF: 0.293 AC: 44562 AN: 151946 Hom.: 6733 Cov.: 32 AF XY: 0.287 AC XY: 21319 AN XY: 74286

Gnomad4 AFR AF: 0.367

Gnomad4 AMR AF: 0.259

Gnomad4 ASJ AF: 0.275

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.268

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.284

Alfa AF: 0.281 Hom.: 8160

Bravo AF: 0.300

Asia WGS AF: 0.256 AC: 895 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	11
Dann	Benign	0.77

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: rs4954368; hg19: chr2-137757933;