rs6902440

Positions:

• chr6-133966598-A-G

Variant summary

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

The NM_004865.4(TBPL1):​c.-45+13173A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,108 control chromosomes in the GnomAD database, including 2,018 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 0.14 (2018 hom., cov: 32)
• Consequence: TBPL1 NM_004865.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.71

Genes affected

TBPL1 (HGNC:11589): (TATA-box binding protein like 1) This gene encodes a member of the TATA box-binding protein family. TATA box-binding proteins play a critical role in transcription by RNA polymerase II as components of the transcription factor IID (TFIID) complex. The encoded protein does not bind to the TATA box and initiates transcription from TATA-less promoters. This gene plays a critical role in spermatogenesis, and single nucleotide polymorphisms in this gene may be associated with male infertility. Alternatively spliced transcript variants have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 3. [provided by RefSeq, Nov 2011]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBPL1	NM_004865.4	c.-45+13173A>G		intron_variant		ENST00000237264.9	NP_004856.1
TBPL1	NM_001253676.2	c.-44-13484A>G		intron_variant			NP_001240605.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBPL1	ENST00000237264.9	c.-45+13173A>G		intron_variant		1	NM_004865.4	ENSP00000237264	P1
	ENST00000674115.1	c.122+13173A>G		intron_variant				ENSP00000501013	P1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21768 AN: 151990 Hom.: 2008 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.0390

Gnomad SAS AF: 0.0851

Gnomad FIN AF: 0.0867

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0860

Gnomad OTH AF: 0.139

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

GnomAD4 genome AF: 0.143 AC: 21813 AN: 152108 Hom.: 2018 Cov.: 32 AF XY: 0.142 AC XY: 10573 AN XY: 74348

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.166

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.0385

Gnomad4 SAS AF: 0.0858

Gnomad4 FIN AF: 0.0867

Gnomad4 NFE AF: 0.0860

Gnomad4 OTH AF: 0.140

Alfa AF: 0.0957 Hom.: 1744

Bravo AF: 0.154

Asia WGS AF: 0.105 AC: 362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.018
DANN	Benign	0.74

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: rs6902440; hg19: chr6-134287736;