rs6902440

Variant names:

• chr6-133966598-A-G
• rs6902440
• NM_004865.4:c.-45+13173A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

LOC128092253 (HGNC:0):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004865.4. 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
	TBPL1	NM_004865.4	MANE Select	c.-45+13173A>G		intron	N/A	NP_004856.1
	LOC128092253	NM_001414965.1	MANE Select	c.122+13173A>G		intron	N/A	NP_001401894.1
	TBPL1	NM_001253676.2		c.-44-13484A>G		intron	N/A	NP_001240605.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBPL1	ENST00000237264.9	TSL:1 MANE Select	c.-45+13173A>G		intron	N/A	ENSP00000237264.3
	ENSG00000288529	ENST00000674115.1	MANE Select	c.122+13173A>G		intron	N/A	ENSP00000501013.1
	TBPL1	ENST00000613034.4	TSL:2	c.-44-13484A>G		intron	N/A	ENSP00000478795.1

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

African (AFR) AF: 0.268 AC: 11091 AN: 41440

American (AMR) AF: 0.166 AC: 2536 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 381 AN: 3472

East Asian (EAS) AF: 0.0385 AC: 199 AN: 5174

South Asian (SAS) AF: 0.0858 AC: 413 AN: 4816

European-Finnish (FIN) AF: 0.0867 AC: 918 AN: 10594

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0860 AC: 5849 AN: 67996

Other (OTH) AF: 0.140 AC: 297 AN: 2116

Alfa AF: 0.103 Hom.: 4466

Bravo AF: 0.154

Asia WGS AF: 0.105 AC: 362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.018
DANN	Benign	0.74
PhyloP100		-2.7
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: rs6902440; hg19: chr6-134287736;