chr2-137000363-T-C

Variant names:

• chr2-137000363-T-C
• rs4954368
• NM_001316349.2:c.140-56057T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001316349.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THSD7B	NM_001316349.2	MANE Select	c.140-56057T>C		intron	N/A	NP_001303278.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THSD7B	ENST00000409968.6	TSL:5 MANE Select	c.140-56057T>C		intron	N/A	ENSP00000387145.1
	THSD7B	ENST00000472720.5	TSL:5	n.*106-56057T>C		intron	N/A	ENSP00000473349.1

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

African (AFR) AF: 0.367 AC: 15220 AN: 41428

American (AMR) AF: 0.259 AC: 3956 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 953 AN: 3468

East Asian (EAS) AF: 0.180 AC: 933 AN: 5172

South Asian (SAS) AF: 0.268 AC: 1291 AN: 4824

European-Finnish (FIN) AF: 0.223 AC: 2357 AN: 10558

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.280 AC: 18999 AN: 67914

Other (OTH) AF: 0.284 AC: 600 AN: 2110

Alfa AF: 0.283 Hom.: 10449

Bravo AF: 0.300

Asia WGS AF: 0.256 AC: 895 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	11
DANN	Benign	0.77
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4954368; hg19: chr2-137757933;