rs460380

Positions:

• chr21-44608947-C-A
• chr21-44608947-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_144991.3(TSPEAR):​c.83-40942G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 152,116 control chromosomes in the GnomAD database, including 40,400 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 0.71 (40400 hom., cov: 33)
• Consequence: TSPEAR NM_144991.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49

Genes affected

TSPEAR (HGNC:1268): (thrombospondin type laminin G domain and EAR repeats) This gene encodes a protein that contains a N-terminal thrombospondin-type laminin G domain and several tandem arranged epilepsy-associated repeats (EARs). A mutation in this gene is the cause of autosomal recessive deafness-98. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSPEAR	NM_144991.3	c.83-40942G>T		intron_variant		ENST00000323084.9	NP_659428.2
TSPEAR	NM_001272037.2	c.-122-40942G>T		intron_variant			NP_001258966.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSPEAR	ENST00000323084.9	c.83-40942G>T		intron_variant		1	NM_144991.3	ENSP00000321987	P1
TSPEAR	ENST00000642437.1	c.*28-40942G>T		intron_variant, NMD_transcript_variant				ENSP00000496535

Frequencies

GnomAD3 genomes AF: 0.714 AC: 108537 AN: 151998 Hom.: 40345 Cov.: 33

Gnomad AFR AF: 0.931

Gnomad AMI AF: 0.669

Gnomad AMR AF: 0.615

Gnomad ASJ AF: 0.701

Gnomad EAS AF: 0.711

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.635

Gnomad OTH AF: 0.733

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

GnomAD4 genome AF: 0.714 AC: 108639 AN: 152116 Hom.: 40400 Cov.: 33 AF XY: 0.709 AC XY: 52674 AN XY: 74334

Gnomad4 AFR AF: 0.931

Gnomad4 AMR AF: 0.614

Gnomad4 ASJ AF: 0.701

Gnomad4 EAS AF: 0.711

Gnomad4 SAS AF: 0.662

Gnomad4 FIN AF: 0.544

Gnomad4 NFE AF: 0.635

Gnomad4 OTH AF: 0.735

Alfa AF: 0.657 Hom.: 38933

Bravo AF: 0.728

Asia WGS AF: 0.707 AC: 2462 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.23
DANN	Benign	0.42

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: rs460380; hg19: chr21-46028864;