11-33081731-C-T

Variant names:

• chr11-33081731-C-T
• rs12365818
• ENST00000528962.1:c.352+9078C>T

Variant summary

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

The ENST00000528962.1(TCP11L1):​c.352+9078C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,014 control chromosomes in the GnomAD database, including 1,441 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 0.13 (1441 hom., cov: 32)
• Consequence: TCP11L1 ENST00000528962.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.292
• Publications: 5 publications found

Genes affected

TCP11L1 (HGNC:25655): (t-complex 11 like 1) Predicted to be involved in signal transduction. Located in microtubule. [provided by Alliance of Genome Resources, Apr 2022]

CSTF3 (HGNC:2485): (cleavage stimulation factor subunit 3) The protein encoded by this gene is one of three (including CSTF1 and CSTF2) cleavage stimulation factors that combine to form the cleavage stimulation factor complex (CSTF). This complex is involved in the polyadenylation and 3' end cleavage of pre-mRNAs. The encoded protein functions as a homodimer and interacts directly with both CSTF1 and CSTF2 in the CSTF complex. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

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 (NFE) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000528962.1. 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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCP11L1	ENST00000528962.1	TSL:3	c.352+9078C>T		intron	N/A	ENSP00000436471.1
	TCP11L1	ENST00000527661.5	TSL:5	n.1617+507C>T		intron	N/A	ENSP00000435667.1
	CSTF3	ENST00000528865.5	TSL:5	n.*55+3301G>A		intron	N/A	ENSP00000435138.1

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19601 AN: 151896 Hom.: 1443 Cov.: 32

Gnomad AFR AF: 0.0564

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.0944

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.129 AC: 19591 AN: 152014 Hom.: 1441 Cov.: 32 AF XY: 0.128 AC XY: 9482 AN XY: 74298

African (AFR) AF: 0.0562 AC: 2331 AN: 41484

American (AMR) AF: 0.135 AC: 2063 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 759 AN: 3472

East Asian (EAS) AF: 0.114 AC: 586 AN: 5160

South Asian (SAS) AF: 0.0934 AC: 450 AN: 4816

European-Finnish (FIN) AF: 0.164 AC: 1728 AN: 10564

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11140 AN: 67964

Other (OTH) AF: 0.147 AC: 309 AN: 2108

Alfa AF: 0.149 Hom.: 2260

Bravo AF: 0.126

Asia WGS AF: 0.0780 AC: 271 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.4
DANN	Benign	0.68
PhyloP100		0.29
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12365818; hg19: chr11-33103277;