11-33081731-C-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCP11L1	ENST00000528962.1	c.352+9078C>T		intron_variant	Intron 2 of 2	3		ENSP00000436471.1
TCP11L1	ENST00000527661.5	n.1617+507C>T		intron_variant	Intron 11 of 12	5		ENSP00000435667.1
CSTF3	ENST00000528865.5	n.*55+3301G>A		intron_variant	Intron 3 of 3	5		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

Gnomad4 AFR AF: 0.0562

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.114

Gnomad4 SAS AF: 0.0934

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.147

Alfa AF: 0.153 Hom.: 1869

Bravo AF: 0.126

Asia WGS AF: 0.0780 AC: 271 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.4
DANN	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12365818; hg19: chr11-33103277;