6-32355752-A-G

Variant names:

• chr6-32355752-A-G
• rs1265758
• NM_001286474.2:c.218-83T>C

Variant summary

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

The NM_001286474.2(TSBP1):​c.218-83T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 1,462,402 control chromosomes in the GnomAD database, including 240,000 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 0.52 (20759 hom., cov: 31)
  • Exomes 𝑓: 0.58 (219241 hom.)
• Consequence: TSBP1 NM_001286474.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.926
• Publications: 36 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286474.2. 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
	TSBP1	NM_001286474.2	MANE Select	c.218-83T>C		intron	N/A	NP_001273403.1
	TSBP1	NM_006781.5		c.218-83T>C		intron	N/A	NP_006772.3
	TSBP1	NM_001286475.2		c.197-83T>C		intron	N/A	NP_001273404.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSBP1	ENST00000533191.6	TSL:1 MANE Select	c.218-83T>C		intron	N/A	ENSP00000431199.1
	TSBP1	ENST00000442822.6	TSL:1	c.197-83T>C		intron	N/A	ENSP00000411164.2
	TSBP1	ENST00000447241.6	TSL:5	c.218-83T>C		intron	N/A	ENSP00000415517.2

Frequencies

GnomAD3 genomes AF: 0.516 AC: 78270 AN: 151806 Hom.: 20738 Cov.: 31

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.623

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.581

Gnomad OTH AF: 0.517

GnomAD4 exome AF: 0.576 AC: 754497 AN: 1310478 Hom.: 219241 AF XY: 0.577 AC XY: 373882 AN XY: 647428

African (AFR) AF: 0.398 AC: 10930 AN: 27466

American (AMR) AF: 0.623 AC: 15690 AN: 25202

Ashkenazi Jewish (ASJ) AF: 0.616 AC: 13774 AN: 22344

East Asian (EAS) AF: 0.444 AC: 15176 AN: 34160

South Asian (SAS) AF: 0.600 AC: 40737 AN: 67912

European-Finnish (FIN) AF: 0.497 AC: 17448 AN: 35102

Middle Eastern (MID) AF: 0.635 AC: 3302 AN: 5202

European-Non Finnish (NFE) AF: 0.584 AC: 606510 AN: 1038842

Other (OTH) AF: 0.570 AC: 30930 AN: 54248

GnomAD4 genome AF: 0.516 AC: 78340 AN: 151924 Hom.: 20759 Cov.: 31 AF XY: 0.511 AC XY: 37931 AN XY: 74244

African (AFR) AF: 0.394 AC: 16325 AN: 41436

American (AMR) AF: 0.546 AC: 8336 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.623 AC: 2160 AN: 3468

East Asian (EAS) AF: 0.473 AC: 2438 AN: 5152

South Asian (SAS) AF: 0.561 AC: 2699 AN: 4814

European-Finnish (FIN) AF: 0.484 AC: 5099 AN: 10538

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.581 AC: 39462 AN: 67928

Other (OTH) AF: 0.516 AC: 1087 AN: 2108

Alfa AF: 0.579 Hom.: 67614

Bravo AF: 0.517

Asia WGS AF: 0.492 AC: 1713 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.17
DANN	Benign	0.38
PhyloP100		-0.93
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: rs1265758; hg19: chr6-32323529; COSMIC: COSV66659018; COSMIC: COSV66659018;