rs485774

Positions:

• chr6-32323177-A-G
• chr6-32323177-A-T

Variant summary

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

The NM_001286474.2(TSBP1):​c.491-40T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 1,404,080 control chromosomes in the GnomAD database, including 101,871 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 0.33 (9624 hom., cov: 32)
  • Exomes 𝑓: 0.38 (92247 hom.)
• Consequence: TSBP1 NM_001286474.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.101

Genes affected

TSBP1 (HGNC:13922): (testis expressed basic protein 1) Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TSBP1-AS1 (HGNC:39756): (TSBP1 and BTNL2 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSBP1	NM_001286474.2	c.491-40T>C		intron_variant		ENST00000533191.6	NP_001273403.1
TSBP1-AS1	NR_136245.1	n.243-42603A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSBP1	ENST00000533191.6	c.491-40T>C		intron_variant		1	NM_001286474.2	ENSP00000431199	A2
TSBP1-AS1	ENST00000645134.1	n.88-67037A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50889 AN: 151982 Hom.: 9611 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.566

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.355

GnomAD3 exomes AF: 0.416 AC: 97258 AN: 233944 Hom.: 21677 AF XY: 0.421 AC XY: 53832 AN XY: 127944

Gnomad AFR exome AF: 0.158

Gnomad AMR exome AF: 0.548

Gnomad ASJ exome AF: 0.568

Gnomad EAS exome AF: 0.381

Gnomad SAS exome AF: 0.467

Gnomad FIN exome AF: 0.303

Gnomad NFE exome AF: 0.413

Gnomad OTH exome AF: 0.408

GnomAD4 exome AF: 0.375 AC: 469680 AN: 1251980 Hom.: 92247 Cov.: 19 AF XY: 0.382 AC XY: 241733 AN XY: 633156

Gnomad4 AFR exome AF: 0.145

Gnomad4 AMR exome AF: 0.534

Gnomad4 ASJ exome AF: 0.555

Gnomad4 EAS exome AF: 0.329

Gnomad4 SAS exome AF: 0.461

Gnomad4 FIN exome AF: 0.306

Gnomad4 NFE exome AF: 0.368

Gnomad4 OTH exome AF: 0.373

GnomAD4 genome AF: 0.335 AC: 50918 AN: 152100 Hom.: 9624 Cov.: 32 AF XY: 0.335 AC XY: 24900 AN XY: 74360

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.446

Gnomad4 ASJ AF: 0.566

Gnomad4 EAS AF: 0.369

Gnomad4 SAS AF: 0.427

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.399

Gnomad4 OTH AF: 0.352

Alfa AF: 0.404 Hom.: 11915

Bravo AF: 0.340

Asia WGS AF: 0.343 AC: 1195 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.8
DANN	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs485774; hg19: chr6-32290954; COSMIC: COSV66658973; COSMIC: COSV66658973;