2-136855017-A-T

Variant names:

• chr2-136855017-A-T
• rs1346731
• NM_001316349.2:c.-35-27127A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001316349.2(THSD7B):​c.-35-27127A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.757 in 152,110 control chromosomes in the GnomAD database, including 43,826 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 0.76 (43826 hom., cov: 32)
• Consequence: THSD7B NM_001316349.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.619
• Publications: 1 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THSD7B	NM_001316349.2	c.-35-27127A>T		intron_variant	Intron 1 of 27	ENST00000409968.6	NP_001303278.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THSD7B	ENST00000409968.6	c.-35-27127A>T		intron_variant	Intron 1 of 27	5	NM_001316349.2	ENSP00000387145.1
THSD7B	ENST00000472720.5	n.-35-27127A>T		intron_variant	Intron 1 of 3	5		ENSP00000473349.1

Frequencies

GnomAD3 genomes AF: 0.757 AC: 115062 AN: 151992 Hom.: 43800 Cov.: 32

Gnomad AFR AF: 0.787

Gnomad AMI AF: 0.688

Gnomad AMR AF: 0.835

Gnomad ASJ AF: 0.827

Gnomad EAS AF: 0.729

Gnomad SAS AF: 0.768

Gnomad FIN AF: 0.701

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.728

Gnomad OTH AF: 0.790

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

GnomAD4 genome AF: 0.757 AC: 115143 AN: 152110 Hom.: 43826 Cov.: 32 AF XY: 0.758 AC XY: 56367 AN XY: 74334

African (AFR) AF: 0.786 AC: 32635 AN: 41498

American (AMR) AF: 0.835 AC: 12757 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.827 AC: 2870 AN: 3472

East Asian (EAS) AF: 0.728 AC: 3764 AN: 5168

South Asian (SAS) AF: 0.769 AC: 3705 AN: 4816

European-Finnish (FIN) AF: 0.701 AC: 7404 AN: 10566

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.728 AC: 49469 AN: 67992

Other (OTH) AF: 0.787 AC: 1661 AN: 2110

Alfa AF: 0.751 Hom.: 5324

Bravo AF: 0.770

Asia WGS AF: 0.742 AC: 2580 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.63
DANN	Benign	0.37
PhyloP100		-0.62
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: rs1346731; hg19: chr2-137612587;