chr6-32323177-A-G

Variant names:

• chr6-32323177-A-G
• rs485774
• NM_001286474.2:c.491-40T>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.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
• Publications: 28 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.437 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.491-40T>C		intron	N/A	NP_001273403.1
	TSBP1	NM_006781.5		c.539-40T>C		intron	N/A	NP_006772.3
	TSBP1	NM_001286475.2		c.470-40T>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.491-40T>C		intron	N/A	ENSP00000431199.1
	TSBP1	ENST00000442822.6	TSL:1	c.470-40T>C		intron	N/A	ENSP00000411164.2
	TSBP1	ENST00000447241.6	TSL:5	c.539-40T>C		intron	N/A	ENSP00000415517.2

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

GnomAD2 exomes AF: 0.416 AC: 97258 AN: 233944 AF XY: 0.421

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 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

African (AFR) AF: 0.145 AC: 4228 AN: 29114

American (AMR) AF: 0.534 AC: 22607 AN: 42340

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 13513 AN: 24340

East Asian (EAS) AF: 0.329 AC: 12691 AN: 38556

South Asian (SAS) AF: 0.461 AC: 36597 AN: 79452

European-Finnish (FIN) AF: 0.306 AC: 15888 AN: 51960

Middle Eastern (MID) AF: 0.555 AC: 2928 AN: 5280

European-Non Finnish (NFE) AF: 0.368 AC: 341353 AN: 927656

Other (OTH) AF: 0.373 AC: 19875 AN: 53282

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

African (AFR) AF: 0.161 AC: 6677 AN: 41512

American (AMR) AF: 0.446 AC: 6808 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.566 AC: 1964 AN: 3468

East Asian (EAS) AF: 0.369 AC: 1906 AN: 5164

South Asian (SAS) AF: 0.427 AC: 2061 AN: 4824

European-Finnish (FIN) AF: 0.296 AC: 3132 AN: 10580

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.399 AC: 27129 AN: 67960

Other (OTH) AF: 0.352 AC: 741 AN: 2108

Alfa AF: 0.386 Hom.: 31547

Bravo AF: 0.340

Asia WGS AF: 0.343 AC: 1195 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.8
DANN	Benign	0.57
PhyloP100		0.10
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs485774; hg19: chr6-32290954; COSMIC: COSV66658973; COSMIC: COSV66658973;