chr2-136959281-G-C

Variant names:

• chr2-136959281-G-C
• rs518614
• NM_001316349.2:c.139+76964G>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.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
• Publications: 0 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.544 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.139+76964G>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.139+76964G>C		intron	N/A	ENSP00000387145.1
	THSD7B	ENST00000472720.5	TSL:5	n.*105+52715G>C		intron	N/A	ENSP00000473349.1

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

African (AFR) AF: 0.194 AC: 8044 AN: 41490

American (AMR) AF: 0.361 AC: 5512 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1762 AN: 3472

East Asian (EAS) AF: 0.0696 AC: 360 AN: 5176

South Asian (SAS) AF: 0.317 AC: 1529 AN: 4816

European-Finnish (FIN) AF: 0.561 AC: 5921 AN: 10556

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.549 AC: 37292 AN: 67958

Other (OTH) AF: 0.391 AC: 826 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.51
PhyloP100		0.055
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: rs518614; hg19: chr2-137716851;