6-32312814-T-C

Variant names:

• chr6-32312814-T-C
• rs9268208
• NM_001286474.2:c.574+2958A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001286474.2(TSBP1):​c.574+2958A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0539 in 146,454 control chromosomes in the GnomAD database, including 361 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 0.054 (361 hom., cov: 29)
• Consequence: TSBP1 NM_001286474.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0850
• Publications: 15 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BS2: High Homozygotes in GnomAd4 at 361 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSBP1	NM_001286474.2	c.574+2958A>G		intron_variant	Intron 22 of 25	ENST00000533191.6	NP_001273403.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSBP1	ENST00000533191.6	c.574+2958A>G		intron_variant	Intron 22 of 25	1	NM_001286474.2	ENSP00000431199.1

Frequencies

GnomAD3 genomes AF: 0.0539 AC: 7893 AN: 146334 Hom.: 361 Cov.: 29

Gnomad AFR AF: 0.0136

Gnomad AMI AF: 0.0509

Gnomad AMR AF: 0.0246

Gnomad ASJ AF: 0.0349

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0708

Gnomad MID AF: 0.0191

Gnomad NFE AF: 0.0925

Gnomad OTH AF: 0.0376

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

GnomAD4 genome AF: 0.0539 AC: 7890 AN: 146454 Hom.: 361 Cov.: 29 AF XY: 0.0494 AC XY: 3529 AN XY: 71456

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0135 AC: 541 AN: 40016

American (AMR) AF: 0.0245 AC: 369 AN: 15064

Ashkenazi Jewish (ASJ) AF: 0.0349 AC: 120 AN: 3442

East Asian (EAS) AF: 0.00 AC: 0 AN: 4974

South Asian (SAS) AF: 0.00 AC: 0 AN: 4598

European-Finnish (FIN) AF: 0.0708 AC: 699 AN: 9872

Middle Eastern (MID) AF: 0.0205 AC: 6 AN: 292

European-Non Finnish (NFE) AF: 0.0924 AC: 6034 AN: 65274

Other (OTH) AF: 0.0373 AC: 76 AN: 2038

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0602 Hom.: 72

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.2
DANN	Benign	0.49
PhyloP100		-0.085
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: rs9268208; hg19: chr6-32280591;